Nonlinear first-pass metabolism of nifedipine in healthy subjects

Publisher Website
Google Scholar
Abstract
1. A dose-range study was carried out with nifedipine (NF) in 11 healthy subjects, who received orally 5, 10 and 20mg in capsules (cap) and 20mg as slow-release tablet. 2. The dose-normalized area under the curve (AUC) of NF showed significant nonlinearity: AUC of 5 mg (cap) was 312 ± 179, of 10 mg (cap) 357 ± 186 and of 20 mg (cap) 424 ± 174 (ng. h/ml). The AUC of the tablet was significantly lower than that of 10 and 20 mg (cap), but not different from 5 mg (cap). 3. The dose-normalized AUC of the pyridine metabolite (M-0) significantly decreased with increasing dose: AUC of 5 mg (cap) was 244 ± 88, of 10 mg (cap) 194 ± 96 and of 20 mg (cap) 120 ± 37 (ng.h/ml). 4. The excretion of M-I (which is ester-hydrolysed M-0) into urine was not different for any of the doses. 5. It is concluded that NF exhibits nonlinear first-pass metabolism, which conco-mitantly affects the formation of M-0, but not that of M-I.