[Pharmacology of a new sleep-inducer, a 1H-1,2,4-triazolyl benzophenone derivative, 450191-S (VIII). Examination and determination of metabolites in human plasma and urine].
Oral administration of 450191-S to humans at 4 mg/man led to the formation of the same plasma metabolites as those found in animals; i.e., M-1, M-2, M-A, M-3 and M-4. Unlike in animals, M-4 was the major metabolite in human plasma for 6 hr after dosing. 450191-S was not found in human plasma after administration of the commonly used dose of 450191-S (1-2 mg/man). The major human urinary metabolite was also M-4, and 44-68% of the dose was excreted as M-4 into 0-24 hr urine. The unchanged 450191-S excreted into the urine was scarcely detectable. Minor metabolites also seemed to be present in the urine, such as the 4OHM-3 conjugate, M-1 and its conjugate, M-2 and its conjugate, M-A and its conjugate, and M-3 and its conjugate. However, all of them together came to not more than 1% of the dose.
Shionogi Research Laboratories, Shionogi & Co., Ltd., Osaka, Japan.
T
T
Yamaguchi
M
M
Nakanishi
M
M
Yamashita
H
H
Matsumoto
M
M
Nakamura
G
G
Kominami
K
K
Iwatani
Y
Y
Nakagawa
M
M
Kono
K
K
Sugeno
D000328:Adult; D008401:Gas Chromatography-Mass Spectrometry; D005965:Glucuronates / Q000378:metabolism; D006801:Humans; D006993:Hypnotics and Sedatives / Q000378:metabolism*; D008297:Male; D014230:Triazoles / Q000378:metabolism*
D005965:Glucuronates; D006993:Hypnotics and Sedatives; D014230:Triazoles; C041075:rilmazafone