Concentration/effect relationship and enantioselective analysis of verapamil in hypertensive patients.
The concentration/effect relationship of verapamil was analyzed in 9 hypertensive patients using concentrations of racemic verapamil and the corresponding decrease in mean arterial blood pressure (MBP) in a sigmoidal Emax model. Concentration/effect data were obtained after a first dose (240 mg sustained release preparation) and at steady state after stepwise dose adjustment to obtain satisfactory BP control (less than 90/150 mm Hg). Emax (MBP) ranged from 15 to 40 mm Hg, and EC50 averaged 81 +/- 40 ng/ml (mean +/- SD). The fraction of S-verapamil in the overall racemic verapamil concentrations was measured in two patients by chiral high-performance liquid chromatography (HPLC) and showed a slight increase at steady state from 12.2 +/- 1.5 to 14.4 +/- 1.4% and from 14.0 +/- 1.3 to 16.3 +/- 0.6%. Concentration/effect curves for S-verapamil concentrations were similar to those obtained with racemic verapamil concentrations.
Harder
S
S
Department Clinical Pharmacology, University Hospital, Frankfurt/Main, Germany.
Thürmann
P
P
Siewert
M
M
Blume
H
H
Rietbrock
N
N
vander Kleijn
J
J
Gierend
M
M
D000284:Administration, Oral; D000328:Adult; D001794:Blood Pressure / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D006973:Hypertension / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D013237:Stereoisomerism; D014700:Verapamil / Q000008:administration & dosage / Q000097:blood* / Q000627:therapeutic use
D014700:Verapamil