I. Vercruysse et al., ENANTIOSELECTIVE INHIBITORY EFFECT OF NICARDIPINE ON THE HEPATIC-CLEARANCE OF PROPRANOLOL IN MAN, Chirality, 6(1), 1994, pp. 5-10
The influence of a single oral dose of 30 mg nicardipine on the pharma
cokinetics of (R)- and (S)-propranolol, given orally as rac-propranolo
l 80 mg, was studied in 12 healthy volunteers. The plasma concentratio
ns were higher for the (S)-enantiomer than for the (R)-enantiomer. The
Cl-o, and the Cl'(intr) of (S)-propranolol were significantly lower t
han the Cl-o and Cl'(intr) of(R)-propranolol The unbound fraction of (
R)-propranolol was significantly higher than that of(S)-propranolol, C
oadministration of nicardipine significantly increased the AUC and C-m
ax 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 ni
cardipine. The enantioselective effect of nicardipine on the metabolic
clearance of propranolol appears to be due to an interaction at the l
evel of the metabolizing enzymes. The effect on blood pressure of rac-
propranolol was little affected when nicardipine was coadministered wi
th rac-propranolol, and its bradycardic effect was reduced. (C) 1994 W
iley-Liss, Inc.