In vivo pharmacokinetics in human volunteers: oral administered guar gum-based colon-targeted 5-fluorouracil tablets

The objective of the present study is to compare the guar gum-based colon-targeted tablets of 5-fluorouracil against an immediate release tablet by in vitro dissolution and in vivo pharmacokinetic studies in human volunteers. Twelve healthy volunteers participated in the study. 5-Fluorouracil was administered at a dose of 50 mg both in immediate release tablet and colon-targeted tablet. On oral administration of colon-targeted tablets, 5-fluorouracil started appearing in the plasma at 6 h, and reached the peak concentration (C, a of 216+/-15 ng/ml) at 7.6+/-0.1 h (T-max), whereas the immediate release tablets produced peak plasma concentration (C-max of 278+/-21 ng/ml) at 0.6+/-0.01 h (T-max). The AUC(0-infinity) for 5-fluorouracil from colon-targeted tablet and immediate release tablet were found to be 617+/-39 and 205+/-21 ng/ml/h, respectively. Colon-targeted tablets showed delayed t(max), delayed absorption time (t(u)), decreased C-max and decreased absorption rate constant when compared to the immediate release tablets. The results of the study indicated that the guar gum-based colon-targeted formulation did not release the drug in stomach and small intestine, but delivered it to the colon resulting in a slow absorption of the drug and making it available for local action in colon. (C) 2003 Elsevier B.V. All rights reserved.