Influence of cholestyramine resin administration on single dose sulindac pharmacokinetics.
Cholestyramine, a nonabsorbable anion exchange resin, has been reported to bind concomitantly administered drugs and decrease their bioavailability. The objective of the study was to determine cholestyramine effect on the plasma concentrations of sulindac and its sulfide metabolite following concurrent and staggered (sulindac 3 hours before cholestyramine) dosing. Six healthy volunteers participated in an open-label, 3-way crossover study. Subjects received 400 mg sulindac orally followed by serial blood sampling for sulindac and sulindac sulfide plasma concentrations over a 24-hour period. During the concurrent phase, 4 g of cholestyramine was coadministered resulting in a decrease (p < 0.05) in the area under the curve (AUC) for sulindac compared to sulindac alone (7.11 +/- 3.25 micrograms-h/ml vs 31.65 +/- 7.94 micrograms-h/ml respectively). Also, the sulindac sulfide AUC decreased (p < 0.05) to 7.26 +/- 4.37 micrograms-h/ml coadministration of both drugs compared to 44.69 +/- 11.81 micrograms-h/ml when sulindac is given alone. When the same doses of each drug were given 3 hours apart, the AUC for sulindac (17.88 +/- 3.69 micrograms-h/ml) and its sulfide metabolite (20.12 +/- 7.46 micrograms-h/ml) were still significantly decreased (p < 0.05) when compared to sulindac given alone (31.65 +/- 7.94 micrograms-h/ml for sulindac and 44.69 +/- 11.81 micrograms-h/ml for sulindac sulfide). Based on the lower AUCs for sulindac and sulindac sulfide, separating sulindac and cholestyramine by 3-hour intervals did not prevent the interaction. It is likely that the enterohepatic recycling features of sulindac may not prevent the interaction with cholestyramine even when the 2 drugs are staggered.
Malloy
M J
MJ
Department of Clinical Pharmacy, Auburn University, Alabama 36849.
Ravis
W R
WR
Pennell
A T
AT
Hagan
D R
DR
Betagari
S
S
Doshi
D H
DH
D000328:Adult; D002792:Cholestyramine Resin / Q000494:pharmacology*; D002851:Chromatography, High Pressure Liquid; D018592:Cross-Over Studies; D005260:Female; D006207:Half-Life; D006801:Humans; D008297:Male; D013440:Sulfides / Q000097:blood; D013450:Sulfones / Q000097:blood; D013467:Sulindac / Q000097:blood / Q000493:pharmacokinetics*
D013440:Sulfides; D013450:Sulfones; D002792:Cholestyramine Resin; D013467:Sulindac