Physiological disposition of verapamil in man

Abstract

14C-D,L-verapamil was administered intravenously (10 mg) and orally (80 mg) to five volunteer patients. Plasma concentrations of verapamil, which were determined by mass fragmentography, declined bi-exponentially with half-lives of the chi-phase ranging from 18 to 35 min and of the beta-phase from 170 to 440 min. The apparent volume of distribution ranged from 270 to 460 litre and plasma clearance from 730 to 1980 ml/min. Following oral administration absorption was almost complete as judged from the area under the curve (AUC) of 14C-activity and cumulative urinary excretion of 14C. After intravenous infusion of verapamil about 80% of the radioactivity administered could be recovered in urine and faeces within 5 d. Despite its almost complete absorption after oral administration verapamil was shown to undergo extensive first pass metabolism as the bioavailability was only 10 to 22%. Rapid biotransformation had occurred as only a small percentage of AUC of 14C was seen to correspond to unchanged verapamil after both intravenous and oral administration.

Stereoselective first‐pass metabolism of highly cleared drugs: studies of the bioavailability of L‐ and D‐verapamil examined with a stable isotope technique.

“…800 ml/min) . The absorption of verapamil following oral administration of an aqueous solution has been shown to be almost complete (Schomerus et al, 1976). Only traces of unchanged verapamil were recovered in urine (Eichelbaum et al, 1979).…”

“…doses of 5 to 10 mg. pass metabolism (Schomerus et al, 1976; Eichel-However, oral doses 10 to 15 times greater than baum et Freedman et al, 1981;i.v. doses are usually required to produce Kates et al, 1981;Anderson et al, 1982; comparable clinical effects (Singh et al, 1983).…”

Potential usefulness of quinine to circumvent the anthracycline resistance in clinical practice

“…Binding of resistance modifiers to serum proteins must also be considered before extrapolating the results of in vitro studies to clinical practice. However, no dramatic difference is registered in the binding of the present resistance modifiers to serum proteins: 90% for verapamil (Schomerus et al, 1976), 75-95% for quinidine (Ochs et al, 1980) and quinine (Silamut et al, 1985). Stability of quinine concentration in patient serum related to its long half-life (10 h) appears also as a propitious property for its use as a circumventing agent of the anthracycline resistance in future clinical studies.…”

Prenatal diagnosis and therapy of fetal heart rate anomalies: With a contribution on the placental transfer of Verapamil

“…Paroxysmal tachycardias are almost exclusively of supraventricular origin. The treatment consists of the use of Verapamil in combination with digitalis to the mother [6,7,8]. This treatment brings about a normalization of the heart rate by inhibiting AV conduction and Prolongation of the refactory time [7].…”