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Klik på et bogstav for at se de begreber, der er forklaringer til.
- ACE-hæmmere: Angiotensin Converting Enzyme hæmmere. ACE-hæmmere nedsætter aktiviteten af renin-angiotensin-aldosteron-systemet ved at hæmme omdannelsen af angiotensin I til II, hvorved universel vasodilatation uden sympatikusaktivering indtræder og medfører fald i blodtrykket. Anvendes typisk mod forhøjet blodtryk og hjerteinsufficiens.
- Antacida: Stoffer der neutraliserer syre produceret i mavesækken. Eller: Syreneutraliserende stoffer, der medfører neutralisering af mavesækkens pH.
- AUC: Area under the curve. Det grafiske areal under en plasmakoncentrations-tids-kurve for et lægemiddel. AUC bruges til at beskrive, hvordan kroppen eksponeres for et givent lægemiddel og anvendes til at estimere biotilgængeligheden og clearence.
- BID: Medicinsk forkortelse for bis in die = to gange dagligt.
- Biotilgængelighed, F: Den del af et oralt administreret lægemiddel, der i forhold til en intravenøs dosis når det systemiske kredsløb. Omfatter også den hastighed, hvormed dette sker. Biotilgængelighed omfatter både absorptionen over tarmvæggen (absorptionen sensu strictiori) og en evt. førstepassagemetabolisme.
- Bredspektret antibiotika: Antibiotika med virkning på et bredt spektrum af mikroorganismer, i modsætning til smalspektrede antibiotika, der kun er virksomme over for specifikke typer af mikroorganismer.
- Clearance (Cl): Forholdet mellem et lægemiddels (eller andet stofs) eliminationshastighed (mængde per tidsenhed) og dets koncentration i plasma (eller blod).
Clearance er konstant, dvs. koncentrations-uafhængig, for stoffer, der elimineres efter en 1. ordens-reaktion.
Clearance bestemmer sammen med fordelingsrummet halveringstiden. Clearance fra forskellige eliminationsorganer er additiv.
- Cmax: Den maksimale koncentration i plasma, der opnås efter lægemiddelindgift.
Ved i.v. indgift er Cmax lig Co, mens Cmax efter peroral indgift oftest først opnås efter 1-2 timer (tmax).
- CYP P450: Cytochrom-P450. Enzymsystem, som metaboliserer adskillige lægemidler via oxidering.
Oxidering udgør den kvantitativt dominerende eliminationsvej for lægemidler. CYP-enzymerne forekommer i særlig høj koncentration i leveren.
- Fald i clearance: Lægemidlet tager længere tid at få renset ud af kroppen.
- Halveringstid, t1/2: Den tid, det tager organismen (efter fordeling) at eliminere halvdelen af den tilbageværende mængde lægemiddel i kroppen.
Størrelsen er konstant og koncentrationsuafhængig for lægemidler med 1. ordens-elimination.
- Hepatisk: Vedr. leveren.
- Hypertension: Forhøjet blodtryk.
- Hypoglykæmi: Lavt blodsukker. Symptomer optræder ofte ved blodsukker lavere end 2,5 mmol/L.
- Hypotension: Lavt blodtryk.
- Hypothyreose: Nedsat funktion af skjoldbruskkirtlen som fører til nedsat dannelse af hormon (thyroxin) og dermed for lavt stofskifte.
- Inducerende lægemiddel: Når et lægemiddel forårsager øget omsætning af et andet lægemiddel via induktion af f.eks. CYP450.
- Induktion: Øget omsætning af et lægemiddel via induktion af f.eks. CYP450.
- INR: International normalized ratio. INR er en standardiseringsmetode til sammenligning af koagulationstider (protrombintider, PT). INR er således et mål for blodets evne til at koagulere.
INR har til formål at minimere forskellene mellem tromboplastinreagenser ved hjælp af en kalibreringsproces, hvor alle kommercielle tromboplastiner sammenlignes med et internationalt referencemateriale.
INR beregnes således: INR=((Patient PT)/(Middel normal PT))^ISI , og fortæller dermed hvor lang koagulationstiden er i forhold til den normale koagulationstid.
- ISI: International Sensitivity Index. Protrombintid målt med forskellige tromboplastiner kan ikke sammenlignes direkte med hinanden, f.eks. fordi sensitiviteten over for koagulationsfaktorer kan variere. For at få koagulationstider, der er så sammenlignelige som muligt, godkendte Verdenssundhedsorganisationen (WHO) i 1983 en standard reference-tromboplastin. Alle producenter af tromboplastin skal kalibrere deres reagens over for WHOs standard. Den fundne værdi betegnes International Sensitivity Index (ISI), og bruges til at beregne INR.
- Iskæmi: Ophævet eller nedsat blodforsyning af et væv i forhold til dets behov.
- Isoenzymer: Forskellige udtryksformer for et enzym. Opstår pga. af forskellige allelle gener. Eksempler ses inden for det lægemiddelomsættende system CYP450, hvor isoenzymer f.eks. er 2D6, 3A4 og 2C9.
- Kasuistik: I lægevidenskab en offentliggjort beskrivelse af et enkelt eller få sygdomstilfælde (casus (lat.): ”tilfælde, sag”).
- Lipidsænkende lægemidler: Lægemidler, der sænker visse af blodets fedtstoffer – kolesterolsænkende.
- Metabolisme: Metabolisme eller stofskifte er en generel betegnelse for den biokemiske omsætning af kemiske forbindelser i den levende organisme og dens celler. Bruges synonymt med biotransformation.
- P-gp: Permeability glycoprotein. P-gp er et cellemembran-protein, som er tilstede i epithelceller i bl.a. tarm, lever og nyrer, hvor det transporterer fremmede substanser fra blodet og ud i hhv. tarmen, galdegange og nyretubuli.
- Plasma: Plasma er den fraktion af blodet, der ikke indeholder celler. Plasma indeholder forskellige næringsstoffer, hormoner, antistoffer, koagulationsfaktorer og salte. 95% af plasma består af vand.
- PO: Per os. Via munden.
- PN medicinering: Pro re nata medicinering. Medicin, der gives efter behov.
- PT: Protrombintid. Tiden, det tager plasma at koagulere, efter tilsætning af tromboplastin (også kaldet tissue factor). Protrombintiden bruges til at vurdere blodets koagulationsevne, og anvendes især til monitorering af antikoagulationsbehandling.
- qd: Quaque die. Hver dag.
- QID: Quater in die. Fire gange dagligt.
- Renal: (af lat. renalis), vedr. nyrerne.
- Respirationsdepression: Respirationsdepression (også kaldet hypoventilation) er når frekvensen eller dybden af respirationen er utiltrækkelig til at opretholde den nødvendige gasudveksling i lungerne.
- Serotonergt syndrom: Et symptomkompleks, der skyldes overstimulering i centralnervesystemet med serotonergt aktive substanser. Symptomerne er muskelrykninger, skælven, kvalme, diarré, sved og forvirring.
- Serum: Plasma uden koagulationsfaktorer.
- SID: Semel in die. Én gang dagligt.
- SmPC: SmPC står for Summary of Product Characteristics, og er det engelske udtryk for produktresumé.
- TID: Ter in die. Tre gange dagligt.
- tmax: Det tidspunkt, hvor den maksimale plasmakoncentration af et lægemiddel indtræder. Des hurtigere absorptionshastighed, des mindre tmax.
- Total clearance: Summen af hepatisk og renal clearance. I hvilken grad disse fraktioner bidrager afhænger af, om lægemidlet primært udskilles renalt eller også undergår fase I (f.eks. via CYP) og fase II (f.eks. glukuronidering) biotransformation i leveren.
- UGT: Uridine 5'-diphospho-glucuronosyltransferase, eller UDP- glucuronosyltransferase. Glucuronyltransferaser er enzymer, som foretager konjugering (glucuronidering) af mange lægemidler og lægemiddelmetabolitter, hvorved de omdannes til stoffer, der er lettere at udskille.
- Vasodilatation: Udvidelse af kar.
- Vasokonstriktion: Sammentrækning af kar.
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Formålet med Interaktionsdatabasen er at gøre behandlingen med lægemidler mere effektiv og sikker, og fremme kvaliteten i patientbehandlingen, herunder bidrage til rationel farmakoterapi. Det har været til hensigt at udvikle et redskab, der er let at anvende i den kliniske hverdag og, hvor der på højt fagligt niveau er skabt konsensus om rekommandationer og beskrivelser af interaktioner mellem lægemidler.
Interaktionsdatabasens primære evidensgrundlag er offentligt publicerede, peer-reviewed original interaktionslitteratur (kliniske studier udført på mennesker og kasuistikker) publiceret i PubMed og Embase.
Der vil således kunne forekomme uoverensstemmelse mellem andre opslagsværker, som er opbygget efter andre principper og evidenskriterier.
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Etableringen af Interaktionsdatabasen var et fælles projekt mellem Danmarks Apotekerforening, Den Almindelige Danske Lægeforening, Dansk Lægemiddel Information A/S og Institut for Rationel Farmakoterapi. En projektleder og 2 farmaceuter stod for opbygningen af databasen bistået af et fagligt videnskabeligt udvalg. Desuden har der været tilknyttet eksperter indenfor forskellige fagområder. Efter en årrække under Sundhedsstyrelsen overtog Lægemiddelstyrelsen i 2015 driften og vedligeholdelsen af databasen.
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Vær opmærksom på, at alle anbefalinger på Interaktionsdatabasen.dk er vejledende.
Hjemmesiden giver desuden ikke oplysninger om bivirkninger ved hvert enkelt præparat. Her henviser vi til indlægssedlen i det enkelte præparat eller til Lægemiddelstyrelsens produktresuméer.
Der kan forekomme bivirkninger, du ikke kan finde informationer om her. Dem vil vi opfordre dig til at indberette til Lægemiddelstyrelsen. Det kan du gøre på:
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I denne database er lægemiddelinteraktion defineret som en ændring i enten farmakodynamikken og/eller farmakokinetikken af et lægemiddel forårsaget af samtidig behandling med et andet lægemiddel.
Interaktionsdatabasen medtager farmakodynamiske interaktioner, der ikke er umiddelbart indlysende additive (fx med forskellig virkningsmekanisme), og som kan have væsentlig klinisk betydning.
Andre faktorer, som interagerer med eller ændrer lægemiddelvirkningen så som næringsmidler (f.eks. fødemidler og kosttilskud) og nydelsesmidler (f.eks. alkohol og tobak), er ikke medtaget. Dog er medtaget lægemiddelinteraktioner med grapefrugtjuice, tranebærjuice og visse naturlægemidler.
Interaktionsdatabasens primære evidensgrundlag er offentligt publicerede, peer-reviewed original interaktionslitteratur (kliniske studier udført på mennesker samt kasuistikker) publiceret i PubMed og Embase. Desuden er interaktioner hvor data er beskrevet i produktresuméer medtaget.
I Interaktionsdatabasen findes fem forskellige symboler:
- Det røde symbol (tommelfingeren, der peger nedad) betyder, at den pågældende præparatkombination bør undgås. Denne anbefaling bliver givet i tilfælde hvor det vurderes, at den kliniske betydning er udtalt, og hvor dosisjustering ikke er mulig, eller hvis der er ligeværdige alternativer til et eller begge af de interagerende stoffer. Det røde symbol vælges også i tilfælde, hvor der vurderes at være ringe dokumenteret effekt af et eller begge stoffer, (hvor anvendelse derfor ikke findes strengt nødvendig), f.eks. for visse naturlægemidler.
- Det gule symbol (den løftede pegefinger) betyder, at kombinationen kan anvendes under visse forholdsregler. Denne anbefaling gives i tilfælde, hvor det vurderes, at den kliniske betydning er moderat til udtalt, samtidig med at den negative kliniske effekt af interaktionen kan modvirkes, enten gennem ned- eller opjustering af dosis, eller ved at forskyde indtagelsestidspunktet for det ene præparat. Anbefalingen gives også, hvis det vurderes, at kombinationen kan anvendes under forudsætning af øget opmærksomhed på effekt og/eller bivirkninger.
- Det grønne symbol (tommelfingeren, der peger opad) betyder, at kombinationen kan anvendes. Denne anbefaling gives i tilfælde, hvor det vurderes, at den kliniske betydning er uvæsentlig eller ikke tilstede.
- Det blå symbol (udråbstegnet) fremkommer i tilfælde, hvor der søges på et specifikt præparat eller en præparatkombination, som ikke findes beskrevet i Interaktionsdatabasen, men hvor der findes andre beskrevne interaktioner mellem stoffer i stofgruppen, som muligvis kan være relevante for søgningen.
- Det grå symbol (spørgsmålstegnet) fremkommer i tilfælde, hvor der er søgt på et præparat eller en præparatkombination, som (endnu) ikke er beskrevet i Interaktionsdatabasen, og hvor der heller ikke findes beskrivelser af andre præparatkombinationer mellem de to stofgrupper. En manglende beskrivelse er ensbetydende med, at Lægemiddelstyrelsen ikke har kendskab til videnskabelige undersøgelser, der undersøger en interaktion mellem den pågældende præparatkombination, og heller ikke til kasuistiske beskrivelser af en mulig interaktion. Der kan også være tale om en kombination, hvor der ikke kan drages konklusioner på baggrund af nuværende viden.
Opdatering af databasens faglige indhold foregår via litteratursøgninger som leveres via Det Kongelige Bibliotek. Litteratursøgningerne er struktureret efter veldefinerede søgekriterier og bliver løbende evalueret. Endvidere foretages yderligere håndsøgning i referencelister som kvalitetssikring af litteratursøgningerne.
Databasen bliver opdateret løbende.
Lægemiddelstyrelsens enhed Regulatorisk & Generel Medicin står for opdatering og vedligehold af Interaktionsdatabasens indhold.
Vedligehold og opdatering af databasen foretages af den faglige arbejdsgruppe, som består af 1 akademisk medarbejder og 2 studerende.
Arbejdsgruppen samarbejder med en deltidsansat speciallæge i klinisk farmakologi omkring den kliniske vurdering af lægemiddelinteraktionerne.
Interaktionsdatabasen er et opslagsværktøj, der beskriver evidensbaserede interaktioner, det vil sige interaktioner, der er dokumenteret ved publicerede kliniske studier og/eller kasuistikker. Der vil således kunne forekomme uoverensstemmelse mellem andre opslagsværker, som er opbygget efter andre principper og evidenskriterier.
Der inkluderes kun interaktioner fra offentligt publicerede, peer-reviewed original interaktionslitteratur (kliniske studier udført på mennesker samt kasuistikker) publiceret i PubMed og Embase. Desuden er interaktioner hvor data er beskrevet i produktresuméer også medtaget. Det tilstræbes at databasen opdateres snarest efter publicering, men der kan forekomme forsinkelser.
Interaktionsdatabasen beskriver interaktioner for markedsførte lægemidler, naturlægemidler samt stærke vitaminer og mineraler. I interaktionsbeskrivelserne skelnes som udgangspunkt ikke mellem forskellige dispenseringsformer. For udvalgte lægemidler skelnes dog mellem dermatologiske og systemiske formuleringer. Handelsnavnene for stærke vitaminer og mineraler, naturlægemidler samt lægemidler som ikke figurerer på medicinpriser.dk (dvs. SAD præparater) kan ikke findes på interaktionsdatabasen.
Interaktionsdatabasen omhandler ikke kosttilskud, vacciner, parenteral ernæring, elektrolytvæsker, lægemidler uden systemisk effekt og priktest (ALK).
Ja, du kan slå både lægemidler, naturlægemidler, stærke vitaminer, mineraler og enkelte frugtjuice op.
Naturlægemidler er en særlig gruppe lægemidler, der typisk indeholder tørrede planter eller plantedele, udtræk af planter eller andre naturligt forekommende bestanddele. Naturlægemidler er i lovgivningen defineret som "lægemidler, hvis indholdsstoffer udelukkende er naturligt forekommende stoffer i koncentrationer, der ikke er væsentligt større end dem, hvori de forekommer i naturen". Naturlægemidler skal godkendes af Lægemiddelstyrelsen inden de må sælges.
Stærke vitaminer og mineraler er en gruppe lægemidler, hvis indholdsstoffer udelukkende er vitaminer og/eller mineraler, og hvor indholdet af vitamin eller mineral er væsentligt højere end det normale døgnbehov hos voksne mennesker. Stærke vitaminer og mineraler kan kun godkendes til at forebygge og helbrede såkaldte mangeltilstande (og altså ikke til at behandle sygdomme). Stærke vitaminer og mineraler må kun sælges i Danmark, hvis de er godkendt af Lægemiddelstyrelsen.
Ja, du kan søge på så mange lægemidler/indholdsstoffer, du ønsker samtidig. Det gør du ved at bruge søgeboksen til højre på forsiden med overskriften ”Søg på flere præparater i kombination”. Her kan du tilføje flere felter med knappen nederst. Hvis du søger på kombinationer med mere end to slags lægemidler/indholdsstoffer, skal du være opmærksom på, at du ikke kun får ét resultat, men et antal 1+1 kombinationer. Et eksempel: Hvis du søger på samtidig brug af en p-pille, et blodtrykssænkende lægemiddel og et sovemiddel, får du 3 mulige resultater:
A: kombinationen af p-pille og blodtrykssænkende lægemiddel
B: kombinationen af p-pille og sovemiddel
C: kombinationen af blodtrykssænkende lægemiddel og sovemiddel
Du får de parvise kombinationer, der er videnskabeligt undersøgt.
Nej, du skal ikke angive dosis (500mg paracetamol) eller interval (2xdaglig), når du skal søge på et præparat eller indholdsstof. Det er kun selve præparatnavnet eller navnet på indholdsstoffet, du skal skrive. Vælg eventuelt bare navnet fra listen.
Det er desværre sådan, at der indtil videre kun kan søges på indholdsstof, når det gælder naturlægemidler.
Dette sker, når du søger på et kombinationspræparat. Når du søger på et kombinationspræparat, får du præsenteret et resultat for hvert af disse indholdsstoffer.
Indholdet i databasen er resultatet af grundige vurderinger af videnskabelige artikler og konklusioner fra humane forsøg. Hvis du kun får én interaktion på trods af, at du har indtastet flere præparater eller indholdsstoffer, skyldes det, at der endnu ikke er beskrevet (eller fundet) interaktioner af de andre indholdsstoffer i den videnskabelige litteratur.
På Lægemiddelstyrelsens hjemmeside, og i månedsbladet Rationel Farmakoterapi, juni 2015.
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Lægemiddelstyrelsen
Axel Heides Gade 1
2300 København S
Tlf.nr 44 88 95 95
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Interaktionsoplysninger
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1. Præparat: Ibumetin - Aktivt indholdsstof: ibuprofen |
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Interaktionsoplysninger for cimetidin og ibuprofen |
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Der er ud fra et farmakokinetísk synspunkt ikke fundet nogen interaktion mellem ibuprofen og cimetidin.
ingen
veldokumenteret
h2-antagonister cimetidin, famotidin, nizatidin, ranitidin, ranitidinbismuthcitrat antiinflamm./antirheum. midler, non-steroide aceclofenac, celecoxib, dexibuprofen, dexketoprofen, diclofenac, diflunisal, etodolac, etoricoxib, flurbiprofen, ibuprofen, indometacin, ketoprofen, ketorolac, lornoxicam, meloxicam, nabumeton, naproxen, parecoxib, phenylbutazon, piroxicam, sulindac, tenoxicam, tiaprofensyre, tolfenamsyre, tolmetin Cimetidin kan hæmme omsætningen af visse NSAID, men hæmningen er så beskeden, at det næppe har nogen klinisk betydning. Der er således ikke fundet nogle klinisk betydningsfulde interaktioner mellem NSAID og H2-antagonister.
Der er i litteraturen ikke lokaliseret yderligere undersøgelser eller kasuistikker, som beskriver h2-antagonisters påvirkning af NSAID.
Litteraturgennemgang - Vis
Piroxicam og cimetidin
Ved kombinationsbehandling med piroxicam og cimetidin viser undersøgelser en stigning i AUC for piroxicam på 16 - 41%, Said SA og Foda AM, 1989; Mailhot C, Dahl SL et al, 1986. I en undersøgelse ses ikke signifikant påvirkning af AUC for piroxicam, Milligan PA, McGill PE et al, 1993.
Piroxicam og ranitidin
Der er ud fra et farmakokinetisk synspunkt ikke fundet nogen interaktion mellem piroxicam og ranitidin, Dixon JS, Lacey LF et al, 1990.
Piroxicam og nizatidin
Der er ud fra et farmakokinetisk synspunkt ikke fundet nogen interaktion mellem piroxicam og nizatidin, Milligan PA, McGill PE et al, 1993.
Flurbiprofen og cimetidin
Ved kombinationsbehandling med flurbiprofen og cimetidin sås en stigning i AUC for flurbiprofen på 13-15 % pga. hæmning af flurbiprofens omsætning, Sullivan KM, Small RE et al, 1986; Small RE, Cox SR et al, 1990.
Flurbiprofen og ranitidin
Der er ud fra et farmakokinetisk synspunkt ikke fundet nogen interaktion mellem flurbiprofen og ranitidin, Sullivan KM, Small RE et al, 1986; Small RE, Cox SR et al, 1990.
Lornoxicam og cimetidin
Et studie med 12 forsøgspersoner viser, at kombination af lornoxicam og cimetidin giver stigning i AUC på 9 % for lornoxicam, Ravic M, Salas-Herrera I et al, 1993. Lornoxicam og ranitidin Der er ud fra et farmakokinetisk synspunkt ikke fundet nogen signifikant interaktion mellem lornoxicam og ranitidin, Ravic M, Salas-Herrera I et al, 1993.
Ibuprofen og cimetidin
Der er i 5 prospektive studier (Ochs HR, Greenblatt DJ et al, 1985; Forsyth DR, Jayasinghe KS et al, 1988; Evans AM, Nation RL et al, 1989; Conrad KA, Mayersohn M et al, 1984; Stephenson DW, Small RE et al, 1988) ikke fundet nogen signifikant interaktion mellem ibuprofen og cimetidin ud fra et farmakokinetisk synspunkt.
Ibuprofen og ranitidin
Der er i 4 prospektive studier ikke fundet nogen signifikant interaktion mellem ibuprofen og ranitidin, Ochs HR, Greenblatt DJ et al, 1985; Stephenson DW, Small RE et al, 1988; Berardi RR, Dressman JB et al, 1988; Small RE, Wilmot-Pater MG et al, 1991.
Ibuprofen og nizatidin
Der er ud fra et farmakokinetisk synspunkt ikke fundet nogen interaktion mellem ibuprofen og nizatidin, Forsyth DR, Jayasinghe KS et al, 1988.
Indomethacin og cimetidin
Ved kombinationsbehandling med indomethacin og cimetidin er der ikke observeret signifikante forandringer i indomethacins farmakokinetik, Delhotal-Landes B, Flouvat B et al, 1988a. Indomethacin og ranitidin
Der er ud fra et farmakokinetisk synspunkt ikke fundet nogen interaktion mellem indomethacin og ranitidin, Muller P, Dammann HG et al, 1989.
Sulindac og cimetidin
Der er ud fra et farmakokinetisk synspunkt ikke fundet nogen statistisk signifikant interaktion mellem sulindac og cimetidin, Delhotal-Landes B, Flouvat B et al, 1988a.
Sulindac og ranitidin
Der er ud fra et farmakokinetisk synspunkt ikke fundet nogen interaktion mellem sulindac og ranitidin, Delhotal-Landes B, Flouvat B et al, 1988a.
Naproxen og cimetidin
Ved kombinationsbehandling med naproxen og cimetidin hos 6 raske forsøgspersoner, sås fald i AUC for naproxen på ca. 21 %, fald i halveringstiden på ca. 50 % og stigning i clearance på ca. 32 %, Vree TB, Biggelaar-Martea M et al, 1993.
Naproxen og ranitidin
Ved kombinationsbehandling med naproxen og ranitidin sås ingen signifikante ændringer i AUC for naproxen, mens t1/2 faldt med 35 %, Vree TB, Biggelaar-Martea M et al, 1993.
Ketoprofen og cimetidin
Der er ud fra et farmakokinetisk synspunkt ikke fundet nogen interaktion mellem ketoprofen og cimetidin, Verbeeck RK, Corman CL et al, 1988.
Tenoxicam og cimetidin
Der er ud fra et farmakokinetisk synspunkt ikke fundet nogen interaktion mellem tenoxicam og cimetidin, Day RO, Geisslinger G et al, 1994.
Meloxicam og cimetidin
Ved kombinationsbehandling med meloxicam og cimetidin sås en stigning i AUC for meloxicam på 10 %, Busch U, Heinzel G et al, 1996.
Ranitidin og diclofenac
Der er ud fra et farmakokinetisk synspunkt ikke fundet nogen interaktion mellem ranitidin og diclofenac, Leucuta A, Vlase L et al, 2004.
Muller P;Dammann HG;Langer M;Leucht U;Simon B, Z Gastroenterol, 1989, 27:83-86; [Ranitidine ameliorates acemetacin and indomethacin-induced changes of the gastroduodenal mucosa, without modifying the pharmacokinetic behavior of both antirheumatic drugs] 12 healthy volunteers participated in this double-blind, randomized, cross-over study. All subjects were given indomethacin (50 mg tid) or acemetacin (60 mg tid) for 6 days in the presence and absence of ranitidine 300 mg at night. At day 6 120 minutes after the last morning dose an endoscopy was performed and the appearance of the gastric and duodenal mucosa was noted. In the indomethacin experiments mean lesion score averaged 2.2 +/- 0.2 (+/- SEM) when placebo was coadministered. In the corresponding acemetacin-series the lesions score was 1.6 +/- 0.1 (+/- SEM). A reduction in mucosal damage occurred in both NSAID- groups when ranitidine 300 mg at night was given concurrently: The mucosal lesions score was reduced to 1.7 +/- 0.2 and to 1.0 +/- 0.1 (+/- SEM), respectively. This protection afforded by ranitidine was significant when compared with placebo (p less than 0.05). In 8 subjects plasma concentrations of acemetacin and indomethacin were determined on day 1 and day 5. The AUC-values of indomethacin and acemetacin in the presence and absence of ranitidine were almost identical when analysed by the paired T-test. The mean plasma concentrations of both antirheumatic agents did not show any difference when coadministered with placebo or ranitidine. Our data suggest that 300 mg ranitidine at night improves the gastroduodenal tolerability of both indomethacin and acemetacin without affecting main pharmacokinetic parameters of both antirheumatics Dixon JS;Lacey LF;Pickup ME;Langley SJ;Page MC, Eur J Clin Pharmacol, 1990, 39:583-586; A lack of pharmacokinetic interaction between ranitidine and piroxicam The effects of piroxicam (40 mg) on the pharmacokinetics of ranitidine (150 mg) and of ranitidine (150 mg bid) on the pharmacokinetics of piroxicam (20 mg) were assessed in two 2-way crossover studies in two groups of 18 healthy male subjects. In the first study there were no statistically significant differences between the pharmacokinetic variables for ranitidine in the presence or absence of piroxicam. The mean maximum plasma concentration (Cmax) was 467 ng.ml-1 for ranitidine alone and 466 ng.ml-1 in the presence of piroxicam: mean area under the plasma concentration vs time curve (AUC) was 2460 h.ng ml-1 and 2551 h.ng ml-1 respectively; and the mean terminal half-life (t 1/2) was 3.6 h and 3.8 h respectively. In the second study there were no statistically significant differences between the pharmacokinetic variables for piroxicam in the presence or absence of ranitidine. The mean Cmax was 2.1 micrograms.ml-1 in the presence of placebo and 2.0 micrograms.ml-1 in the presence of ranitidine respectively; mean AUC was 133 h.microgram ml-1 and 137 h.microgram ml-1 respectively, and the mean t 1/2 was 53.6 h and 54.5 h respectively Ravic M;Salas-Herrera I;Johnston A;Turner P;Foley K;Rosenow DE, Postgrad Med J, 1993, 69:865-866; A pharmacokinetic interaction between cimetidine or ranitidine and lornoxicam Cimetidine 400 mg twice daily significantly increased serum concentrations and reduced apparent oral clearance of lornoxicam 8 mg twice daily in 12 healthy volunteers. Ranitidine 150 mg twice daily produced no significant changes in lornoxicam pharmacokinetics Conrad KA;Mayersohn M;Bliss M, Br J Clin Pharmacol, 1984, 18:624-626; Cimetidine does not alter ibuprofen kinetics after a single dose Cimetidine does not slow the disappearance of ibuprofen from the serum after a single dose in healthy male volunteers. This suggests that no change in ibuprofen dosing is necessary when cimetidine is co- administered Forsyth DR;Jayasinghe KS;Roberts CJ, Eur J Clin Pharmacol, 1988, 35:85-88; Do nizatidine and cimetidine interact with ibuprofen? The potential for interaction between ibuprofen and two histamine H2- receptor blocking drugs--nizatidine and cimetidine--was investigated in six healthy male volunteers aged 20 to 25 years. Each subject received placebo, nizatidine 300 mg and cimetidine 800 mg orally at 9.00 p.m. daily for six doses in three randomised treatment periods separated by eight days. On the third day of each treatment period ibuprofen 400 mg was administered at the same time and venous blood samples were taken at intervals throughout the night and subsequently up to 84 h after administration. There was no difference in the area under the plasma concentration-time curve, rate of absorption or half-life of elimination of ibuprofen between the three treatments. The elimination half-life of ibuprofen on placebo was 2.04 h. The elimination half-life of nizatidine on ibuprofen was 1.72 h and that of cimetidine was 3.54 h. The latter is higher than previously reported in normal subjects. It is concluded that neither H2-blocker affects the kinetics of ibuprofen in man Stephenson DW;Small RE;Wood JH;Willis HE;Johnson SM;Karnes HT;Rajasekharaiah K, Clin Pharm, 1988, 7:317-321; Effect of ranitidine and cimetidine on ibuprofen pharmacokinetics The purpose of this study was to determine whether ranitidine or cimetidine can effect the pharmacokinetics of ibuprofen at steady-state conditions. Sullivan KM;Small RE;Rock WL;Cox SR;Willis HE, Clin Pharm, 1986, 5:586-589; Effects of cimetidine or ranitidine on the pharmacokinetics of flurbiprofen The effect of oral cimetidine or ranitidine on the pharmacokinetics of the nonsteroidal anti-inflammatory agent flurbiprofen was studied. Nine healthy volunteers participated in the study. The subjects were divided into three groups, and each group alternated therapy with each of the following treatments: flurbiprofen 200 mg (two 100-mg tablets), flurbiprofen 200 mg plus ranitidine 150 mg two times daily for seven days before and for two days after receiving flurbiprofen, and flurbiprofen 200 mg plus cimetidine 300 mg four times a day for seven days before and for two days after receiving flurbiprofen. Blood samples were collected at time zero and at various intervals during a 48-hour period. Serum flurbiprofen concentrations were determined by high-performance liquid chromatography. No significant differences in elimination rate constant, peak concentration, time to peak concentration, volume of distribution, or elimination half-life were noted among treatments. The difference in area under the curve (AUC) in subjects treated with flurbiprofen alone and in those treated with flurbiprofen plus cimetidine was significant. Two subjects experienced gastric upset; one case was apparently caused by cimetidine, and the other was likely caused by flurbiprofen. Although a significant increase in AUC was observed in subjects receiving flurbiprofen plus cimetidine, the interaction is probably not clinically important Small RE;Wilmot-Pater MG;McGee BA;Willis HE, Clin Pharm, 1991, 10:870-872; Effects of misoprostol or ranitidine on ibuprofen pharmacokinetics The purpose of this study was to determine whether misoprostol or ranitidine therapy affects the pharmacokinetic profile of ibuprofen. Berardi RR;Dressman JB;Elta GH;Szpunar GJ, Biopharm Drug Dispos, 1988, 9:337-347; Elevation of gastric pH with ranitidine does not affect the release characteristics of sustained release ibuprofen tablets The effect of elevating gastric pH on the release characteristics of a single unit sustained release (SR) ibuprofen tablet (MOTRIN-SR, Upjohn) was evaluated in 12 young, healthy men. Using a randomized crossover- type design, each subject received three treatments--ibuprofen SR 800 mg, ranitidine 300 mg followed by ibuprofen SR 800 mg, and conventional ibuprofen tablets (2 x 400 mg). Gastric pH, which was monitored radiotelemetrically, was maintained above pH 6 for at least 4 h after pretreatment with ranitidine. In absence of ranitidine, the pH remained mostly below pH 3. Serum levels of ibuprofen were measured for 24 h and urine was collected for 48 h after each treatment. Similarity of the serum levels after the two treatments with ibuprofen SR 800 mg indicated that the release of ibuprofen was unaffected by elevation in gastric pH. Comparison of profiles with the immediate release dosage form indicated that dose dumping did not occur in any subject Said SA;Foda AM, Arzneimittelforschung, 1989, 39:790-792; Influence of cimetidine on the pharmacokinetics of piroxicam in rat and man The influence of cimetidine on piroxicam plasma levels and pharmacokinetic parameters was studied in both rats and healthy volunteers. In male rats, intravenous injection of piroxicam (6 mg/kg) in animals pretreated with cimetidine (50 mg/kg intramuscular) resulted in plasma piroxicam concentrations significantly higher than those of animals which received piroxicam alone. The plasma half-life (1/2) of piroxicam in male rats was about 8.3 h and it was increased to 20.74 h by cimetidine pretreatment. The mean area under piroxicam plasma level- time curves was significantly (p less than 0.01) higher in case of rats pretreated with cimetidine compared with those treated with piroxicam alone. Similar results were obtained in male healthy volunteers, where administration of a single dose of piroxicam (20 mg orally) to subjects who received cimetidine (200 mg 3 times a day orally) resulted in plasma piroxicam concentrations significantly higher than those of subjects treated with piroxicam alone. The t1/2 of piroxicam was increased from 37.36 to 52.86 h with cimetidine administration. Also the mean area under piroxicam plasma level-time curves was significantly (p less than 0.05) increased by cimetidine administration Small RE;Cox SR;Adams WJ, J Clin Pharmacol, 1990, 30:660-664; Influence of H2 receptor antagonists on the disposition of flurbiprofen enantiomers The effect of oral cimetidine or ranitidine on the pharmacokinetics of the R and S enantiomers of the nonsteroidal anti-inflammatory drug flurbiprofen and its major metabolite, 4´-hydroxyflurbiprofen, was evaluated. Nine healthy volunteers participated in a randomized crossover design study with the following treatments: (A) flurbiprofen 200 mg; (B) flurbiprofen 200 mg plus ranitidine 150 mg bid for 7 days before and for 2 days after receiving flurbiprofen and (C) flurbiprofen 200 mg plus cimetidine 300 mg qid for 7 days before and for 2 days after receiving flurbiprofen. Blood and urine samples were collected at various intervals during a 48-hour period. These samples were assayed stereospecifically for flurbiprofen and its metabolite. Small but statistically significant differences in the terminal elimination rate constant (K), maximum peak serum drug concentration (Cmax), time to reach peak concentration (tmax), oral clearance (Cl/F) and area under the curve (AUC) were noted for flurbiprofen enantiomers. No significant treatment*isomer interactions were observed, indicating that neither cimetidine nor ranitidine interacted stereospecifically with flurbiprofen. Cimetidine, but not ranitidine, resulted in small (less than or equal to 15%) but statistically significant changes in flurbiprofen pharmacokinetic parameters. The interaction between H2- antagonists and flurbiprofen is unlikely to be clinically important Ochs HR;Greenblatt DJ;Matlis R;Weinbrenner J, Clin Pharmacol Ther, 1985, 38:648-651; Interaction of ibuprofen with the H-2 receptor antagonists ranitidine and cimetidine The influences of cimetidine and ranitidine on single-dose ibuprofen kinetics were evaluated. Thirteen healthy subjects took a single, 600 mg oral dose of ibuprofen on three occasions: in the control state without drug coadministration; during concurrent dosing with cimetidine, 1.2 gm/day; and during concurrent dosing with ranitidine, 150 mg twice daily. Compared with the control state, cimetidine increased the peak serum ibuprofen concentration (64 vs. 56 micrograms/ml), but the value during ranitidine dosing (57 micrograms/ml) was indistinguishable from the control value. There were no significant differences between control, cimetidine, and ranitidine conditions in ibuprofen elimination t1/2 (2.1, 2.1, and 2.0 hours, respectively). Overall there was a significant difference among the control, cimetidine, and ranitidine conditions in ibuprofen oral clearance (52.8, 48.3, and 54.1 ml/min, respectively), but individual differences in cimetidine vs. control and between ranitidine vs. control were not statistically significant. The impairment of ibuprofen clearance by cimetidine is small, and ranitidine had no detectable effect on ibuprofen kinetics. These findings should be further validated during chronic dosing with ibuprofen Busch U;Heinzel G;Narjes H;Nehmiz G, J Clin Pharmacol, 1996, 36:79-84; Interaction of meloxicam with cimetidine, Maalox, or aspirin Meloxicam is a new enol carboxamide nonsteroidal antiinflammatory drug (NSAID). Preclinical studies have indicated that it possesses a high antiinflammatory potency and a low ulcerogenic potency. This open, randomized, crossover study was conducted to examine the effects of aspirin, the antacid Maalox (Rhone-Poulenc Rorer, Cologne, Germany), and cimetidine on the pharmacokinetics and bioavailability of a single oral dose of meloxicam 30 mg in healthy male volunteers. Plasma concentrations of meloxicam were determined and subjected to noncompartmental pharmacokinetic analysis. Meloxicam was well tolerated, and concomitant treatment with cimetidine or Maalox had little or no effect on the plasma concentration-time curves, maximum plasma concentration (Cmax), or the area under the plasma concentration- time curve (AUC0-infinity) of meloxicam. Concurrent treatment with aspirin increased plasma concentrations of meloxicam, increasing Cmax by approximately 25% and AUC0-infinity by 10%. These differences were not considered to be clinically relevant, and no adjustments of meloxicam dose should be required with coadministration of aspirin, Maalox, or cimetidine Evans AM;Nation RL;Sansom LN, Br J Clin Pharmacol, 1989, 28:143-149; Lack of effect of cimetidine on the pharmacokinetics of R(-)- and S(+)- ibuprofen 1. To investigate the effect of cimetidine on the pharmacokinetics of R(-)- and S(+)-ibuprofen, six healthy male volunteers received orally 800 mg racemic ibuprofen both in the drug-free state (control phase, C) and on the second day of a 3 day course of oral cimetidine, 1 g daily (treatment phase, T). The two phases (14 days apart) were randomised in a balanced cross-over manner. 2. The plasma concentrations of R(-)- and S(+)-ibuprofen were measured by high-performance liquid chromatography (h.p.l.c.). The protein binding of the enantiomers was assessed in a selection of plasma samples from each volunteer. Following alkaline hydrolysis of glucuronide conjugates, the urinary recoveries of ibuprofen and its major metabolites were measured by h.p.l.c. 3. There was no difference (P greater than 0.05, two-tailed Student´s t-test; data expressed as mean +/- s.d.) between C and T phases in the total area under the plasma concentration-time curve of R(-)-ibuprofen (C 4514 +/- 1063 mg 1(-1) min vs T 4665 +/- 1435 mg 1(-1) min) and S(+)- ibuprofen (C 6460 +/- 1063 mg 1(-1) min vs T 6886 +/- 1207 mg 1(-1) min). Similarly, for each enantiomer, there was no difference between the two phases in the terminal half-life, the maximum plasma concentration or the time of its occurrence. 4. Cimetidine treatment had no effect (P greater than 0.05) on the time-averaged percent unbound in plasma of R(-)-ibuprofen (C 0.419 +/- 0.051% vs T 0.435 +/- 0.060%) and S(+)-ibuprofen (C 0.643 +/- 0.093% vs T 0.633 +/- 0.053%). 1. There was no difference (P>0,05) in the percentage of the administered dose recovered in the urine as ibuprofen plus metabolites (C 84,9 +/- 7,3% vs T 87,6 +/- 3,9%).The results indicate that the pharmacokinetics of R (-) - and S(+) -ibuprofen after a single oral dose of racemic ibuprofen were not influenced by concurrent cimetidine administration. Day RO;Geisslinger G;Paull P;Williams KM, Br J Clin Pharmacol, 1994, 37:79-81; Neither cimetidine nor probenecid affect the pharmacokinetics of tenoxicam in normal volunteers The effect of pretreatment with cimetidine (1 g day-1, 7 days) and of probenecid (1 g twice daily, 4 days) on the pharmacokinetics of tenoxicam (single oral dose, 20 mg) was studied in six healthy volunteers. Cmax was increased significantly when tenoxicam was given with probenecid (2.8 micrograms ml-1 alone, 3.5 micrograms ml-1 after probenecid; P < 0.005). No other pharmacokinetic parameters were altered significantly by either drug. It is concluded that neither cimetidine nor probenecid affects the pharmacokinetics of tenoxicam in a clinically important way Leucuta A;Vlase L;Farcau D;Nanulescu M, Rom J Gastroenterol , 2004, d, 13:306-308; No effect of short term ranitidine intake on diclofenac pharmacokinetics The pharmacokinetics of diclofenac sodium in healthy volunteers was evaluated to determine if previously repeated doses of ranitidine inhibited the metabolism of the non-steroidal anti-inflammatory drug. Diclofenac sodium 50 mg (tablets) in combination with ranitidine 150 mg (tablets) were administered to 14 healthy human volunteers in a two treatment study design, separated by 5 days in which the ranitidine alone was administrated in single p.o. doses twice daily. Plasma concentrations of diclofenac were determined during a 12 hour period following drug administration. Diclofenac plasma concentrations were determined by a validated RP-HPLC method. Pharmacokinetic parameters were calculated with compartmental and non-compartmental analysis. In the two periods of treatments, the mean peak plasma concentrations Cmax were 1503.9 ng/ml (diclofenac alone) and 1742.5 ng/ml (diclofenac and ranitidine). The time taken to reach the peak, Tmax, was 0.85 hrs, and 0.82 hrs, respectively. The areas under the curve (AUC0-6) were 1479.9 ng x hr/ml and 1650.3 ng x hr/ml, respectively. Statistically insignificant difference was observed in these pharmaco-kinetic parameters of diclofenac sodium when administered alone or after 5 days of treatment with ranitidine. The experimental data did not suggest any consistent effects of ranitidine upon the pharmacokinetics of diclofenac sodium Delhotal-Landes B;Flouvat B;Liote F;Abel L;Meyer P;Vinceneux P;Carbon C, Clin Pharmacol Ther, 1988, a, 44:442-452; Pharmacokinetic interactions between NSAIDs (indomethacin or sulindac) and H2-receptor antagonists (cimetidine or ranitidine) in human volunteers The reciprocal effects on pharmacokinetic parameters after a single oral dose of the nonsteroidal antiinflammatory drugs (NSAIDs) indomethacin and sulindac and repeated oral doses of the H2-receptor antagonists cimetidine and ranitidine were determined in two groups of nine healthy subjects each (indomethacin and sulindac groups). Administration of NSAIDs increased the AUC and decreased the oral clearance and apparent volume of distribution of the H2-receptor antagonists without modifying their t1/2. Urinary data and observed modifications in ranitidine and cimetidine metabolites seem to justify a greater increase of H2-receptor antagonist bioavailability with indomethacin (p less than 0.05) than with sulindac (NS). The administration of ranitidine significantly reduced the sulindac volume of distribution without modifying its clearance, which caused an increase in the maximum concentration and a decrease in the t1/2 (p less than 0.05). The effects of cimetidine on the two NSAIDs were more intense than the effect of ranitidine: the decrease in sulindac volume of distribution (p less than 0.02) was accompanied by a significant reduction in sulindac clearance (p less than 0.05). AUC and urinary amounts of sulindac's sulfone metabolite were decreased. These results show that NSAIDs increased the bioavailability of H2-receptor antagonists, and that the latter drugs decrease the volume of distribution of NSAIDs. Furthermore, cimetidine modifies the oxidation metabolism of sulindac Verbeeck RK;Corman CL;Wallace SM;Herman RJ;Ross SG;Le Morvan P, Eur J Clin Pharmacol, 1988, 35:521-527; Single and multiple dose pharmacokinetics of enteric coated ketoprofen: effect of cimetidine The effect of cimetidine on the single and multiple dose pharmacokinetics of enteric coated ketoprofen was studied in 12 healthy volunteers. Each subject completed two 8-day study treatment periods: either ketoprofen alone (100 mg p.o. twice daily), or co-administered with cimetidine (600 mg twice daily). tlag, Cmax, tmax, t1/2, and k for ketoprofen were not significantly different between single and multiple dose administration. AUC of ketoprofen was slightly but significantly larger following multiple (21.2 micrograms.h.ml-1) as compared to single dose administration (19.0 micrograms.h.ml-1). As a result, plasma clearance of ketoprofen was slightly but significantly reduced following multiple dose administration (80.6 ml/min vs 89.3 ml/min). Cimetidine had no effect on the single or multiple dose pharmacokinetics of enteric coated ketoprofen. Total 12-h urinary recovery of ketoprofen (mostly in the form of ketoprofen glucuronide) was 83.5% of the dose following single dose administration and was significantly greater following multiple dose administration (93.1%). Again cimetidine co-administration had no effect on the single and multiple dose urinary recovery. The results of this study show that cimetidine is not affecting the oral pharmacokinetics of enteric coated ketoprofen Milligan PA;McGill PE;Howden CW;Kelman AW;Whiting B, Eur J Clin Pharmacol, 1993, 45:507-512; The consequences of H2 receptor antagonist--piroxicam coadministration in patients with joint disorders A randomised crossover study was performed in subjects with rheumatoid arthritis (or other arthropathies) to investigate if any alteration in the steady pharmacokinetics of the NSAID piroxicam (a drug which is extensively metabolised via cytochrome P450) or its major metabolites occurred as a result of coadministering either cimetidine or nizatidine. Twelve females and 2 males with mean age, weight, and albumin concentrations of 58 years, 61 kg, and 40 g.L-1 respectively, completed the study. Comparisons were made between the following parameters: plasma piroxicam AUCs [AUC0-24(P)], plasma 5- hydroxypiroxicam AUCs [AUC0-24(5-OHP)], the ratio of these i.e. AUC0- 24(5-OHP):AUC0-24(p), the % piroxicam daily dose excreted in urine as 5- hydroxypiroxicam (before and after glucuronidase incubation); and the mean of the steady state trough piroxicam, and 5-hydroxypiroxicam concentrations (obtained during each study phase in addition to the wash-out period). A statistically significant difference as a result of initiating either cimetidine or nizatidine was obtained only for the ratio AUC0-23(5-OHP):AUC0-24(P). This was indicative of a weak potential to inhibit piroxicam hydroxylation. No clinically significant alteration in the steady state pharmacokinetics of piroxicam occurred in these subjects as a result of cimetidine or nizatidine coadministration. Consequently it is unlikely that any adverse events would arise from these combinations Mailhot C;Dahl SL;Ward JR, Pharmacotherapy, 1986, 6:112-117; The effect of cimetidine on serum concentrations of piroxicam To evaluate the effect of cimetidine on serum concentrations of piroxicam, we administered a single 20-mg oral dose of piroxicam to 10 healthy male volunteers on 2 occasions. The first was given on day 1 of the study and the second on day 15, 7 days after starting cimetidine 300 mg orally 4 times a day. Nineteen blood samples were drawn for 7 days after each piroxicam dose to characterize its pharmacokinetics. Piroxicam was analyzed by high-performance liquid chromatography. The mean piroxicam elimination rate constants (Kel), elimination half- lives, and area under the serum concentration-time curves (AUC) were as follows (mean +/- standard deviation): (formula; see text) Data were analyzed with a Wilcoxon matched-pairs, signed-ranks, two-tailed statistical test. Although the increase in AUC was statistically significant, it was of low amplitude (mean 15%) and is probably not clinically significant. The results of this study suggest that cimetidine does not significantly alter the elimination kinetics of a single dose of piroxicam in young healthy males. Additional investigation is needed to confirm these findings in other patient populations Vree TB;Biggelaar-Martea M;Verwey-van Wissen CP;Vree ML;Guelen PJ, Int J Clin Pharmacol Ther Toxicol, 1993, 31:597-601; The effects of cimetidine, ranitidine and famotidine on the single-dose pharmacokinetics of naproxen and its metabolites in humans We studied the effects of cimetidine, ranitidine and famotidine on the kinetics of naproxen. The mean t1/2 beta of naproxen in 6 subjects was 25.7 +/- 5.4 h (range 16 to 36). Naproxen acyl glucuronide accounts for 50.9 +/- 6.9% of the dose, its isomerized isoglucuronide for 6.8 +/- 2.6%, O-desmethylnaproxen acyl glucuronide for 14.3 +/- 4.1% and its isoglucuronide for 5.5 +/- 1.5% (n = 6). Naproxen (1.3 +/- 1.1%) and O- desmethylnaproxen (0.6 +/- 0.4%) are excreted in negligible amounts. Cimetidine, ranitidine and famotidine all reduced significantly the t1/2 beta of naproxen by 50% from 25 h to 13 h and the t1/2 alpha from 4.0 h to 1.1 h. No effect of the H2 antagonists was observed on the absorption of naproxen. They also reduced the Vss of naproxen by 50%. The amount of naproxen acyl glucuronide, naproxen isoglucuronide and O- desmethylnaproxen acyl glucuronide excreted in the urine, remained unchanged, 60%, 7%, and 14% respectively
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