Premium
Enantioselective disposition of oral amlodipine in healthy volunteers
Author(s) -
Laufen Heinrich,
Leitold Máagtyá Ags
Publication year - 1994
Publication title -
chirality
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.43
H-Index - 77
eISSN - 1520-636X
pISSN - 0899-0042
DOI - 10.1002/chir.530060704
Subject(s) - amlodipine , chemistry , enantiomer , pharmacology , oral administration , pharmacokinetics , chromatography , stereochemistry , medicine , blood pressure
Plasma concentrations of (R)‐ and (S)‐amlodipine were measured after single oral administrations to 18 healthy volunteers of 20 mg amlodipine racemate. The contribution of the pharmacologically active (S)‐enantiomer to the concentrations of total amlodipine (sum of enantiomers) was significantly higher than that of the inactive (R)‐enantiomer, with mean values of 47% R to 53% S for the C max and 41% R to 59% S for the AUC (range between 24% R:76% S and 50% R:50% S). The oral clearance of the active (S)‐form was subject to much less intersubject variation (25% CV) than that of the inactive (R)‐form (52% CV). (R)‐Amlodipine was more rapidly eliminated from plasma than (S)‐amlodipine, with mean terminal half‐lives of 34.9 h (R) and 49.6 h (S). The terminal half‐lives of total amlodipine (mean 44.2 h) were strongly correlated with—and thus highly predictive for—the half‐lives of the (S)‐enantiomer. It is proposed that the observed enantioselectivity of oral amlodipine is due to differences in the systemic blood clearance of the enantiomers. © 1994 Wiley‐Liss, Inc.