THE ROLE OF GASTRIC-EMPTYING IN THE ABSORPTION AND METABOLISM OF NIFEDIPINE GIVEN IN A MODIFIED RELEASE PELLET FORMULATION

Plasma drug concentrations after a single oral administration of a modified release pellet formulation of nifedipine (20 mg) were measured in 18 healthy male volunteers after a light breakfast. The distribution of the radiolabelled pellets in the gastrointestinal tract was followed by gamma scintigraphy. The time for 50% gastric emptying ranged from 74 to 254 min (median 127 min), which is in good agreement with values reported for other multiparticulate formulations. In some subjects, periods of gastric stasis were observed, which may have been due to the inhibitory effect of nifedipine on gastric muscle contraction. Substantial spreading of the pellets occurred in both the small intestine and the colon, although in the majority of cases there was re-grouping at the ileo-caecal junction, prior to entry into the large bowel. The mean ( +/- SD) C(max) was 36 +/- 16 ng/ml (range 8.4-70.0 ng/ml), achieved 2-12 h post-dose (median t(max) 3 h). The pharmacokinetic data were consistent with twice daily dosage. Extended gastric residence may be an advantage for a modified release formulation. However, for nifedipine, a drug which undergoes a significant first-pass metabolism, slow gastric emptying may lead to a reduced systemic bioavailability as a result of the gradual presentation of the drug to enzymes on first pass through the intestine and liver.