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Reduced verapamil clearance during long‐term oral administration
Author(s) -
Shand David G,
Hammill Stephen C,
Aasen Lin,
Pritchett Edward L C
Publication year - 1981
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1038/clpt.1981.223
Subject(s) - verapamil , medicine , term (time) , pharmacology , administration (probate law) , oral administration , calcium , physics , quantum mechanics , political science , law
Plasma concentrations of verapamil and its metabolite, norverapamil, were measured in six patients with supraventricular tachycardia after the first and seventh dose of a regimen consisting of 120 mg every 8 hr by mouth. Steady state was reached by the seventh dose and the area under the concentration‐time curve (AUC) at steady state (1999 ± 435[SD] ng/ml · hr) was greater than that after the first dose (788 ± 224, P < 0.001). This unexpected cumulation was associated with prolongation of verapamil half‐life (t½) from 2.75 ± 1.14 to 4.52 ± 1.10 hr. Norverapamil AUC also rose from 1225 ± 405 to 2312 ± 963 ng/ml/hr during the attainment of steady stale. We conclude that verapamil cumulates to a greater extent than predicted from its t½, due to reduction in hepatic clearance. Clinical Pharmacology and Therapeutics (1981) 30, 701–703; doi: 10.1038/clpt.1981.223