Kinetic Disposition and Hemodynamic Effects of Tetrandrine in Anesthetized Dogs

The kinetic disposition and hemodynamic effects of tetrandrine, 13 mg/kg i.v., over 30 s were studied in five anesthetized dogs during continuous monitoring of the ECG and systemic arterial pressure. Repeated determinations of cardiac output (CO) and pulmonary capillary wedge pressure (PCWP) were made via a flow-directed thermodilution catheter in the pulmonary artery. Blood samples were drawn at intervals for determination of plasma tetrandrine or erythrocyte binding of the drug. Maximal reductions in mean and diastolic arterial pressures of 23 ± 4% were observed within 5 min of the drug infusion without a change in systolic pressure. CO was increased maximally 52% and systemic resistance reduced 51% at 10 min, gradually returning to baseline values in 1–2 h. PCWP was increased transiently at 5–10 min. The PR interval was prolonged slightly without alteration in the R-R interval, QRS, or QTc. Changes in MAP and PR interval were correlated significantly with plasma tetrandrine concentrations over time, which followed a two-compartment kinetic model with a distribution t½ of 7 min and an elimination t½ of 88 min. The apparent volume of distribution at steady state was 57 L/kg. Plasma tetrandrine was >90% bound to plasma proteins, and ~44% of whole blood tetrandrine was associated with erythrocytes. Tetrandrine is a potent arteriolar vasodilator drug with slight effects on AV conduction, but without significant negative inotropic effects in anesthetized dogs.