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The developmental change of the intrinsic clearance (Clint) and the hepatic clearance (ClH) 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 Clint increased with the day of gestation, remarkably between the 19th and 21st day of gestation, showing nearly the same developmental profile as the Vmax. The Clint 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 ClH showed the similar developmental profile to the Clint. The ClH 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 ClH on the 20th and 21st day of gestation was about 30% of the corresponding values of the fetal tissue clearance (Clf) from the in vivo data using isolated fetuses. The similarity between the ClH/Clf ratio and the PPBA glucuronide/biliary excretion ratio indicated that the ClH from the in vitro data corresponded with that in the in vivo condition.

journal of pharmacobio-dynamics

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.