DEVELOPMENTAL CHANGE IN CLEARANCE OF GLUCURONIDE OF p-PHENYLBENZOIC ACID FROM IN VITRO KINETIC PARAMETERS AND ITS CORRELATION WITH CLEARANCE FROM IN VIVO IN FETUS OF RAT
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The developmental change of the intrinsic clearance (Cl_<int>) and the hepatic clearance (Cl_H) for the glucuronidated p-phenylbenzoic acid (PPBA) by uridine 5'-phosphoglucronic acid-glucuronyltransferase (UDPGT) in liver of rat fetus was investigated. The UDPGT activity was stimulated by 225% by Brij 58 which is a detergent. The Cl_<int> increased with the day of gestation, remarkably between the 19th and 21st day of gestation, showing nearly the same developmental profile as the V_<max>. The Cl_<int> in a whole liver on the 21st day of gestation was 246-fold and 7.0-fold higher than those on the 15th and 19th day of gestation, respectively. The Cl_H showed the similar developmental profile to the Cl_<int>. The Cl_H on the 21st day of gestation was 48.7 times and 6.7 times those on the 17th and 19 the day of gestation, respectively. The Cl_H on the 20th and 21st day of gestation was about 30% of the corresponding values of the fetal tissue clearance (Cl_f) from the in vivo data using isolated fetuses. The similarity between the Cl_H/Cl_f ratio and the PPBA glucuronide/biliary excretion ratio indicated that the Cl_H from the in vitro data corresponded with that in the in vivo condition.
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関連論文
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- DEVELOPMENTAL CHANGE IN CLEARANCE OF GLUCURONIDE OF p-PHENYLBENZOIC ACID FROM IN VITRO KINETIC PARAMETERS AND ITS CORRELATION WITH CLEARANCE FROM IN VIVO IN FETUS OF RAT
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