Oral administration of nifedipine (20 and 30 mg tablets) to six volunteers was associated with a bioavailability of 0.43 and the presence of its nitropyridine analogue in the plasma. This metabolite was present in only trace amounts in samples taken from the same volunteers following i.v. administration of nifedipine. The peak plasma concentrations and area under the plasma concentration‐time curve suggest that the nitropyridine analogue is a major, first pass, metabolite of nifedipine.

The plasma pharmacokinetics of nifedipine and the formation of its metabolites have been studied in volunteers under conditions which would affect the activity of the cytochrome P-450 system. The pharmacokinetics of a 10-mg capsule of nifedipine were not significantly different between smokers and non-smokers of similar age. After pretreatment with cimetidine, which inhibits the activity of cytochrome P-450, the peak plasma concentration and area under the plasma-time concentration curve for nifedipine were increased by a mean 84%. In contrast, pre-treatment with ranitidine which has little effect on cytochrome P-450, did not significantly alter nifedipine pharmacokinetics. Smoking does not contribute significantly to the variability in nifedipine pharmacokinetics. However, the interaction between nifedipine and cimetidine, but not ranitidine, may be of clinical importance.

1 The trans-hepatic extraction of nifedipine during steady state infusion was studied in six patients undergoing cardiac catheterisation for suspected coronary disease. 2 Mean extraction ratio across the liver was 0.64 but hepatic clearance accounted for a mean of only 65% of total body clearance. 3 These results are consistent with the liver as the major site of metabolism of nifedipine, but also suggest that significant metabolism occurs outside the liver.

1 The pharmacokinetics of a novel 20 mg biphasic release tablet of nifedipine were compared with the conventional 10 mg capsule and 20 mg sustained release preparations in healthy volunteers. The influence of food and posture on the pharmacokinetics of the biphasic tablet were studied. 2 In the fasting state, the time to peak concentration of nifedipine was not significantly different between the 20 mg biphasic and 20 mg sustained release tablets, but plasma concentrations were higher between 2 and 4 h after the biphasic tablet. The terminal elimination half-lives of the two formulations were similar. 3 In subjects who fed prior to nifedipine administration there was no significant difference between either the peak plasma concentration or terminal half-life of the biphasic tablet and two 10 mg capsules of nifedipine. 4 When the biphasic preparation was given after a standard breakfast, the time to peak plasma concentration was significantly longer and the terminal half-life shorter than when given in the fasting state. 5 The dissolution characteristics of the biphasic tablet were influenced by prior administration of food to an extent which may be of clinical significance during twice daily administration.

No abstract