Amosulalol, a combined alpha and beta adrenoceptor antagonist: kinetics after intravenous and oral doses.

Amosulalol kinetic studies were conducted in seven subjects who received 0.16 mg/kg iv and in 18 subjects who received 12.5, 25, 50, 100, or 150 mg by mouth. Plasma levels of amosulalol after intravenous dosing declined biphasically and fitted a two-compartment model. Kinetics were as follows: coefficients A = 0.85 +/- 0.09 microgram/ml and B = 0.22 +/- 0.01 microgram/ml; rate constants alpha = 2.78 +/- 0.24 hr-1 and beta = 0.25 +/- 0.01 hr-1; elimination rate constants, k12 = 1.36 +/- 0.17 hr-1, k21 = 0.78 +/- 0.06 hr-1, and kel = 0.88 +/- 0.06 hr-1; terminal phase volume of distribution = 0.75 +/- 0.06 l/kg; clearance = 8.09 +/- 0.54 l/hr; AUC = 1.22 +/- 0.09 microgram . hr/ml; and t1/2 alpha = 0.26 +/- 0.02 hr and t1/2 beta = 2.8 +/- 0.1 hr. After single oral doses, amosulalol peak plasma levels were generally reached within 2 to 4 hr. Maximum plasma concentrations and AUC increased in a dose-dependent manner, whereas t1/2 were about 5 hr (range 4.4 to 5.7 hr) at each dose. Systemic availability of amosulalol was about 100% as determined by the ratio of AUC after oral and intravenous dosing. These results suggest that amosulalol is well absorbed and is little affected by first-pass metabolism.