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РЖ ВИНИТИ 34 (BI48) 96.07-04Т2.43

Effect of temperature in perfusate on local hepatic disposition of BOF-4272, a new xanthine oxidase inhibitor [Text] / Masuhiro Nishimura [et al.] // Biol. and Pharm. Bull. - 1995. - Vol. 18, N 7. - P980-983 . - ISSN 0918-6158
Перевод заглавия: Влияние температуры перфузата на распределение в [перфузируемой] печени нового ингибитора ксантиноксидазы BOF-4272
Аннотация: The effect of temperature on the local hepatic disposition of BOF-4272 [('+-')-8-(3-methoxy-4-phenylsulfinylphenyl)pyrazolo[1,5-a]-1,3,5- triazine-4-olate], a new drug used to treat hyperuricemia, was investigated by means of a perfusion experiment following the pulse input into the portal vein of rat, in which the temperature of the perfusate was changed from 37'ГРАДУС'C down to 4'ГРАДУС'C. The same perfusion experiment was also attempted using bovine serum albumin (BSA) as a reference substance to compare with the hepatic disposition of BOF-4272. The elution time profiles of BOF-4272 and BSA from the liver into the hepatic vein were evaluated by moment analysis. The recovery ratio (F[H]) and the mean transit time (t[H]) of BOF-4272 were 22.8'+-'3.3% and 0.111'+-'0.008 min at 37'ГРАДУС'C, respectively. Both F[H] and t[H] significantly increased with the decrease in the temperature of the perfusate, 3 times and 2 times greater at 4'ГРАДУС'C than at 37'ГРАДУС'C, respectively. The F[H] and t[H] of BSA were 98.3'+-'4.5% and 0.129'+-'0.013 min at 37'ГРАДУС'C, respectively. These parameters of BSA were independent of temperature, while those of BOF-4272 showed a definite dependency on temperature. A new estimation method for the elimination rate constant (k[c]) and the partition ratio (k') in the dispersion model was developed by rearranging the theoretical equations of F[H] and t[H]. The index for the elimination (k[c]) of BOF-4272 decreased with the decrease in temperature, while the index for the distribution (k') increased with the decrease in temperature. This result shows that the metabolism (or the biliary excretion) decreased and the distribution increased with a decrease in temperature, indicating that the hepatic metabolizing pathway which is presumably temperature-dependent is blocked, and the blocked portion of BOF-4272 thus returns back to the perfusate at the low temperature

ГРНТИ	34.45.21

ВИНИТИ 341.45.21.35.15
Рубрики: ГИПОУРИНЕМИЧЕСКИЕ СРЕДСТВА
КСАНТИНОКСИДАЗЫ ИНГИБИТОРЫ
BOF-4272
РАСПРЕДЕЛЕНИЕ
ПЕРФУЗИРУЕМАЯ ПЕЧЕНЬ
ТЕМПЕРАТУРА
КРЫСЫ

Доп.точки доступа:
Nishimura, Masuhiro; Yamaoka, Kiyoshi; Yasui, Hiroyuki; Naito, Shinsaku; Nakagawa, Terumichi

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