THE EFFECT OF COLESTIPOL AND CHOLESTYRAMINE ON IBUPROFEN BIOAVAILABILITY IN MAN

The purpose of this study was to determine whether a concomitant singl e oral dose of one of the anion exchange resins colestipol hydrochlori de (10 g) or cholestyramine (8 g) administered with ibuprofen (400 mg) would alter the bioavailability of this non-steroidal anti-inflammato ry agent. The study was performed according to a randomized three-way crossover design in six healthy male volunteers. After dosing, serial blood samples were collected for a period of 10 h. Plasma harvested fr om blood was analysed for ibuprofen by a sensitive high-performance li quid chromatographic method. There were no significant differences bet ween colestipol treatment and control for peak plasma concentration (C -max), time to peak concentration (T-max, area under the plasma concen tration-time curve (AUC), mean residence time (MRT), elimination rate constant (K-el), or elimination half-life (t(1/2)). Cholestyramine tre atment resulted in a significant decrease in AUC (26%,.4%, p < 0.01) a nd a significant increase in T-max (80%, p < 0.01) and MRT (20.2%, p < 0.05). Cholestyramine administration showed no significant effect on the K-el, and t(1/2) values. A significant correlation was obtained be tween the increase in MRT and the increase in T-max. The confidence in tervals (90%) of the mean values of the pharmacokinetic parameters (AU C(0-infinity), and C-max) for the colestipol : control ratio were well within the acceptable range of 100 +/- 20 whereas those for the chole styramine : control ratio were outside it. Colestipol treatment was fo und to be bioequivalent to the control treatment by Schuirmann's two o ne-sided t tests, while cholestyramine treatment was found to be bioin equivalent. The results indicate a lack of interaction between ibuprof en and colestipol and a potential significant interaction (decrease in rate and extent of absorption of ibuprofen) between cholestyramine an d ibuprofen in patients receiving concurrent therapy.