Mitsuyoshi Nakashima

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 μg/ml and B = 0.22 ± 0.01 μg/ml; rate constants α = 2.78 ± 0.24 hr−1 and β = 0.25 ± 0.01 hr−1; elimination rate constants, kl2 = 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 μg · hr/ml; and t½α = 0.26 ± 0.02 hr and t½β = 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 t½s 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.