The effect of colestipol and cholestyramine on ibuprofen bioavailability in man

The purpose of this study was to determine whether a concomitant single oral dose of one of the anion exchange resins colestipol hydrochloride (10 g) or cholestyramine (8 g) administered with ibuprofen (400 mg) would alter the bioavailability of this non‐steroidal anti‐inflammatory 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 from blood was analysed for ibuprofen by a sensitive high‐performance liquid chromatographic method. There were no significant differences between colestipol treatment and control for peak plasma concentration (Cmax), time to peak concentration (Tmax), area under the plasma concentration—time curve (AUC), mean residence time (MRT), elimination rate constant (Kel), or elimination half‐life (t1/2). Cholestyramine treatment resulted in a significant decrease in AUC (26%, p< 0.05) and Cmax (34.4%, p <0.01) and a significant increase in Tmax (80%, p < 0.01) and MRT (20.2%, p < 0.05). Cholestyramine administration showed no significant effect on the Kel and t1/2 values. A significant correlation was obtained between the increase in MRT and the increase in Tmax. The confidence intervals (90%) of the mean values of the pharmacokinetic parameters (AUCO–∞ and Cmax) for the colestipol : control ratio were well within the acceptable range of 100 ± 20, whereas those for the cholestyramine : control ratio were outside it. Colestipol treatment was found to be bioequivalent to the control treatment by Schuirmann's two one‐sided t tests, while cholestyramine treatment was found to be bioinequivalent. The results indicate a lack of interaction between ibuprofen and colestipol and a potential significant interaction (decrease in rate and extent of absorption of ibuprofen) between cholestyramine and ibuprofen in patients receiving concurrent therapy.