INVESTIGATION OF NIFEDIPINE ABSORPTION IN DIFFERENT REGIONS OF THE HUMAN GASTROINTESTINAL (GI) TRACT AFTER SIMULTANEOUS ADMINISTRATION OF C-13-NIFEDIPINE AND C-12-NIFEDIPINE

Objective: To evaluate the absorption of nifedipine in man from four d ifferent sites of the gastrointestinal tract. Methods: On separate occ asions, nifedipine solution was administered locally to the stomach, t he small intestine and two sites in the colon in 4 healthy male volunt eers (age 29-34 y weight 73-82 kg, nonsmokers) using a remote controll ed drug delivery device (HF-capsule). In order to assess absolute and relative bioavailabilities, an intravenous infusion was given on a sep arate occasion and all treatments were accompanied by a simultaneous o ral dose of a stable-isotope labelled nifedipine solution. This allowe d to minimise the influence of intra-individual variability. Plasma sa mples were collected up to 24 h post dose and faeces for 72 h. A new m ethod of analysis of nifedipine in plasma and faeces using gas chromat ography with mass-selective detection (GCMS) was employed. Results: Di ssolved nifedipine was found to enter the systemic circulation complet ely along the intestine, being absorbed from jejunum to colon. Absorpt ion was less rapid from the colon than from the upper part of the gut, but this was not associated with a decrease in absorption and/or bioa vailability: Absolute bioavailability, calculated from the normalised AUC values, ranged from 42 to 56%, and bioavailability relative to ora l solution was 100 to 126% (medians of the application sites). Conclus ion: The absence of an absorption window in the intestinal tract sugge sts that nifedipine is well suited for use in controlled-release formu lations.