Premium
Amosulalol, a combined alpha and beta adrenoceptor antagonist: Kinetics after intravenous and oral doses
Author(s) -
Nakashima Mitsuyoshi,
Asano Masaharu,
Ohguchi Sadao,
Hashimoto Hisakuni,
Seki Takashi,
Miyazaki Mitsuhiro,
Takenaka Toichi
Publication year - 1984
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.1984.201
Subject(s) - volume of distribution , pharmacokinetics , dosing , chemistry , antagonist , oral administration , pharmacology , kinetics , dose–response relationship , medicine , endocrinology , receptor , physics , quantum mechanics
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, k l2 = 1.36 ± 0.17 hr −1 , k 21 = 0.78 ± 0.06 hr −1 , and k el = 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. Clinical Pharmacology and Therapeutics (1984) 36, 436–443; doi: 10.1038/clpt.1984.201