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Enantioselective inhibitory effect of nicardipine on the hepatic clearance of propranolol in man
Author(s) -
Vercruysse Isabelle,
Belpaire Frans,
Wynant Pascal,
Massart Désiré L.,
Dupont Alain G.
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.530060104
Subject(s) - chemistry , nicardipine , propranolol , enantioselective synthesis , inhibitory postsynaptic potential , pharmacology , biochemistry , endocrinology , organic chemistry , neuroscience , psychology , calcium , catalysis , medicine
The influence of a single oral dose of 30 mg nicardipine on the pharmacokinetics of (R)‐ and (S)‐propranolol, given orally as rac ‐propranolol 80 mg, was studied in 12 healthy volunteers. The plasma concentrations were higher for the (S)‐enantiomer than for the (R)‐enantiomer. The Cl o and the Cl′ intr of (S)‐propranolol were significantly lower than the Cl o and Cl′ intr of (R)‐propranolol. The unbound fraction of (R)‐propranolol was significantly higher than that of (S)‐propranolol. Coadministration of nicardipine significantly increased the AUC and C max and significantly decreased the Cl o and Cl′ intr for unbound drug of (R)‐ and (S)‐propranolol. These changes were more important for (R)‐ than for (S)‐propranolol. The protein binding was not altered by nicardipine. The enantioselective effect of nicardipine on the metabolic clearance of propranolol appears to be due to an interaction at the level of the metabolizing enzymes. The effect on blood pressure of rac ‐propranolol was little affected when nicardipine was coadministered with rac ‐propranolol, and its bradycardic effect was reduced. © 1994 Wiley‐Liss, Inc.