[Nifedipine pharmacokinetics in patients with exertion-induced stenocardia after its single and long-term...

A study of the causes of tolerance to antianginal effect of nifedipine++, conducted in 12 patients with angina of effort, examined serum pharmacokinetics of nifedipine++ and its primary metabolite (puridine analogue of nifedipine++), after a single 20 or 30 mg dose and at the end of a treatment course (20-40 mg 3-4 times daily for 2 to 6 months). In addition, the effect of nifedipin treatment on nonspecific microsomal hepatic oxidase activity was assessed by means of the antipyrin test. Pharmacokinetics of both unchanged nifedipin and its primary metabolite showed no change through the nifedipin course, suggesting that tolerance to the antianginal effect of nifedipin may be based on altered systemic pharmacologic response rather than altered pharmacokinetics of nifedipin. Nifedipin treatment caused no induction or inhibition of nonspecific microsomal hepatic oxidase activity in the patients so the drug may be expected to have no substantial effect on pharmacokinetics, and hence, efficacy, of combined drugs that are eliminated by oxidation inside the liver.