Pharmacokinetics and metabolism of nifedipine

Abstract

Nifedipine is almost completely absorbed from the gastrointestinal tract as shown by plasma levels after sublingual, oral, and rectal administration. Because of presystemic metabolism, the bioavailability is about 56% to 77%. After oral administration of 10 mg, the mean plasma concentration of nifedipine reaches maximum values of 160 +/- 49 micrograms/liter after 30 to 60 minutes. After 8 hours, the mean concentration drops to 3.4 +/- 1.2 micrograms/liter. After intravenous administration (0.015 mg/kg) biphasic elimination occurs, the half-life of the alpha-phase being about 13 minutes and of the beta-phase 1.26 +/- 0.55 hours in healthy volunteers. After oral administration of higher doses (40 mg) and after continuous infusion over 24 hours, a third phase with a half-life of about 8 hours can be seen. The apparent volume of distribution of the central compartment (Vce) is 0.294 +/- 0.1 l/kg, and the total body clearance amounts to 0.45 +/- 0.1 liter/hr . kg. Nifedipine is eliminated from the body by hepatic metabolism to the major metabolites 2,6-dimethyl-4-(2-nitrophenyl)-5-methoxycarbonyl-pyridine-3-carboxylic acid (M I) and the corresponding 2-hydroxymethyl-pyridinecarboxylic acid (M II). Methods for the quantitative detection of unchanged nifedipine in the presence of the pyridine analog in plasma (HPLC) and of the main metabolites in plasma and urine (GLC) have been developed. A simple semiquantitative method for detecting metabolites in urine (HPTLC) can be used to monitor patient compliance.