The effect of the concurrent administration of sucralfate on the absorption of a single dose of ibuprofen was studied in nine normal volunteers using a random crossover design. Each participant received a single 600-mg dose of ibuprofen for the control phase, and a 600-mg dose of ibuprofen following 5 g of sucralfate given in 1-g divided doses for the treatment phase. Blood samples were obtained at regular intervals for 12 hours following the administration of ibuprofen, and pharmacokinetic and statistical analyses were performed. Analysis of time to peak serum concentration, maximum serum concentration, elimination rate constant, and half-life showed no significant difference between the control and treatment phases. Mean total area under the curve for ibuprofen decreased by 11.8% in the treatment phase, but this decrease was not statistically significant. The concurrent administration of sucralfate did not significantly alter the absorption of a single 600-mg dose of ibuprofen in healthy subjects

Sucralfate has been reported to protect the gastroduodenal mucosa against a variety of agents and is known to adsorb bile salts. Since gastrointestinal side effects can seriously compromise the efficacy of nonsteroidal anti-inflammatory drug therapy, and since it seems reasonable to assume that sucralfate may adsorb nonsteroidal anti- inflammatory drugs, the influence of sucralfate on the pharmacokinetic parameters of naproxen was assessed in 12 healthy volunteers. To do so, the pharmacokinetic profile of naproxen, administered alone or with sucralfate, singly or repeatedly (twice daily for five days), was compared. No significant difference was observed with any pharmacokinetic parameter between the single administration of naproxen alone or with sucralfate. However, a significantly lower maximum plasma concentration was attained with the repeated administration of naproxen in combination with sucralfate, compared with the repeated administration of naproxen alone. When single- and multiple-dose administration were compared, significant differences were observed in the maximum plasma concentration and the cumulative area under the curve. These results suggest an accumulation of naproxen after five days´ administration. This accumulation, however, is not altered by the administration of sucralfate. The results of this study suggest that when naproxen is administered with sucralfate, only a delay in naproxen´s absorption may occur, confirmed by a lower maximum plasma concentration, a longer time to reach the maximum plasma concentration, a similar elimination half-life, and equivalence in bioavailability. The clinical importance of such a delay has yet to be proved; however, it is unlikely that the clinical efficacy of naproxen will be altered, since the amount of drug absorbed remains the same

Compliance to nonsteroidal anti-inflammatory drug therapy can be compromised by gastrointestinal side effects. To overcome this problem, food, antacid, or sucralfate are often co-administered with nonsteroidal anti-inflammatory drugs. Three studies were conducted on three groups of 12 volunteers in order to determine the influence of food or sucralfate on the pharmacokinetics of naproxen and ketoprofen. In a crossover experimental design, the first group received a single dose (50 mg) of ketoprofen with and without sucralfate (2 g). The second group received single (100 mg) and multiple (100 mg twice daily for 5 days) doses of enteric-coated ketoprofen with and without food. The third group received single (500 mg) and multiple (500 mg twice daily) doses of naproxen with and without sucralfate. Multiple blood samples were drawn and analyzed by high-pressure liquid chromatography. Short- and long-term pharmacokinetic parameters were determined. Results in group 1 showed that neither ketoprofen bioavailability nor maximal plasma concentration and time to reach maximal concentration were affected by the administration of sucralfate. However, in group 2 absorption of ketoprofen was markedly affected by food. In the presence of food, maximal plasma concentration decreased from 10.7 to 6.3 micrograms/ml after single-dose administration and 12.1 to 8.0 micrograms/ml after multiple-dose administration. The time to reach maximal plasma concentration was also modified by food, increasing from 2.8 to 7.1 hours after single-dose and 2.8 to 7.6 hours after multiple- dose administration. Food caused a significant decrease in the bioavailability of ketoprofen (over 40 percent) following both single- dose (23.8 versus 13.1 micrograms.hour/ml) and multiple-dose (29.3 versus 16.8 micrograms.hour/ml) administration. Results obtained in group 3 showed that sucralfate reduced the absorption rate constant of naproxen, from 1.7 to 1.2 hours-1 and from 1.5 to 0.7 hour-1 following single- and multiple-dose administration, respectively. However, bioavailability of naproxen was not affected by sucralfate administration. Overall, these studies have shown that sucralfate does not alter the pharmacokinetics of naproxen and ketoprofen; the amount of drug absorbed remains constant. However, plasma concentrations of ketoprofen after single- and multiple-dose administration were greatly affected by food, with a decrease of greater than 40 percent in bioavailability

AIMS: Since patients who regularly take NSAIDS may use sucralfate because of its cytoprotective properties, we examined the influence of this compound on the pharmacokinetics of diclofenac. METHODS: Potassium diclofenac (105 mg) was administered orally to eighteen healthy male volunteers with or without a 5-day pre-treatment with sucralfate (2000 mg twice daily). Blood samples were collected at intervals post-dose and serum concentrations of diclofenac were determined by reverse-phase h.p.l.c. RESULTS: Pre-treatment with sucralfate significantly decreased both the AUC(0,8 h) [2265 ng h ml-1 (geometric mean) (range 1815-2827) vs 1821 ng h ml-1 (1295-2562)] and the Cmax [1135 ng ml-1 (geometric mean) (range 898-1436) 701 ng ml-1 (501-981)] with no significant delay in absorption [tmax 1.0 h (median) (range 0.5-2.0) vs 1.0 h (0.5-4.0)]. CONCLUSIONS: The short-term treatment of healthy male volunteers with sucralfate decreases potassium diclofenac bioavailability. These findings suggest that either an appropriate increase in the diclofenac intake or the use of another gastric mucosa protector must be adopted

The effects of sucralfate on the rate and extent of absorption of ketoprofen, indomethacin, and naproxen were investigated in healthy volunteers. Six volunteers each received sucralfate (2 g) half an hour before a ketoprofen (50 mg) capsule, and, on another occasion, a ketoprofen (50 mg) capsule alone according to a 2 X 2 Latin square pattern of administration. The same design was used for studies with indomethacin (50 mg) capsules and naproxen (500 mg) tablets. Sucralfate decreased significantly (p less than 0.05) the maximum plasma concentrations (Cmax) of ketoprofen, indomethacin, and naproxen. Although the time necessary to attain Cmax (tmax) for the three drugs tended to increase, only for indomethacin was this increase significant. Sucralfate decreased significantly the rate of absorption (ka) of naproxen and indomethacin, but not that of ketoprofen; it had no significant effect on the elimination half-life and area under the plasma concentration as a function of time curves (AUC0----infinity) of the three drugs. Sucralfate thus decreases the Cmax and increases the tmax of ketoprofen, indomethacin, and naproxen without affecting their bioavailabilities

The possible interaction between sucralfate (Ulcogant, CAS 54182-58-0) on the one hand and diclofenac (CAS 15307-86-5) and piroxicam (CAS 36322-90-4) on the other hand was investigated in two groups each consisting of twelve healthy volunteers. The AUC (0-t) was calculated at 1670 +/- 492 ng/ml x h for diclofenac alone and at 1817 +/- 682 ng/ml x h for diclofenac plus sucralfate. The mean AUC (0-t) for piroxicam alone was 91 +/- 19 micrograms/ml x h whilst that for piroxicam plus sucralfate was 91 +/- 20 micrograms/ml x h. The mean relative bioavailability was 116% for diclofenac plus sucralfate compared to diclofenac alone, and 100% for piroxicam plus sucralfate compared to piroxicam alone. Thus there is no interaction between sucralfate and diclofenac resp. piroxicam

This randomized, multiple cross-over pharmacokinetic study was undertaken to determine if food or sucralfate alter the bioavailability of the active S(+) enantiomer of ibuprofen. Eleven healthy adult male volunteers were given three single 600-mg doses of ibuprofen (separated by 1 week) administered either in a fasting state, after a standardized breakfast, or with sucralfate 1 g. The main outcome measures were area under the concentration (AUC), maximum peak plasma concentration (Cmax), and time to reach peak concentration (tmax) for total, S(+), and R(-) enantiomer serum ibuprofen levels, drawn up to 10 hours after dosing. The AUC for R(-) ibuprofen was significantly lower than S(+) ibuprofen in all three treatment groups. The treatments had no different effects on AUC for S(+), R(+), or total ibuprofen. There was no difference in the ratio of S(+):R(-) enantiomers across different treatment groups, but the intersubject variability was significant (P < .05). The S(+) ibuprofen Cmax was greater than the R(-) ibuprofen Cmax for all treatment groups (P < .05). Sucralfate reduced the peak concentration of both S(+) and R(-) enantiomers when compared with fasting (P < .05). There was a slight but nonsignificant increase in the mean time to achieve peak concentration of both S(+) and R(-) enantiomers. Neither food nor sucralfate has a significant effect on ibuprofen enantiomer pharmacokinetics, but interindividual variability contributes significantly to the variability of enantiomer bioavailability