scholarly journals Studies on the Metabolic Fate of Leukotriene Antagonist ONO-1078. (2). Absorption, Distribution, Excretion and Effects on Drug Metabolizing Enzyme Activities after Repeated Oral Administration to Rats.

1993 ◽  
Vol 8 (1) ◽  
pp. 27-38
Author(s):  
Masatsune ISHIDO ◽  
Kimio SHIBAKAWA ◽  
Masafumi SAWADA ◽  
Hideki AISHITA
Keyword(s):  
Oral Administration ◽  
Enzyme Activities ◽  
Metabolic Fate ◽  
Drug Metabolizing Enzyme ◽  
Leukotriene Antagonist ◽  
Metabolizing Enzyme

The Influence of Phenobarbitone on Maternal and Perinatal Hepatic Drug-metabolizing Enzymes in the Rat

1975 ◽  
Vol 53 (6) ◽  
pp. 1147-1157 ◽  
Author(s):  
J. U. Bell ◽  
M. M. Hansell ◽  
D. J. Ecobichon
Keyword(s):  
Endoplasmic Reticulum ◽  
Enzyme Activities ◽  
Morphological Changes ◽  
Smooth Endoplasmic Reticulum ◽  
Transplacental Passage ◽  
Hepatic Drug ◽  
Rat Pups ◽  
Drug Metabolizing Enzyme ◽  
Metabolizing Enzyme ◽  
Conjugating Enzyme

Phenobarbitone (PB) (75 mg/kg) was administered orally for three consecutive days to pregnant or lactating rats at different pre- and postnatal stages in order that the perinatal animals would receive the agent either by transplacental passage or via the milk. Control animals received equivalent volumes of saline. The dams, fetuses, and pups were killed 24 h after the last dose. Hepatic p-nitroanisole O-demethylase (OD), carboxylesterase (CE), and bromosulfophthalein–glutathione (BSP–GSH) conjugating enzyme activities in a 12 100 g – 20 min supernatant of a 20% w/v homogenate were measured. The morphology of the developing rat liver in the absence and presence of PB was examined by electron microscopy.The results demonstrated that the transplacental passage of PB to rat fetuses at term or 3 days prepartum had no effect on either the hepatic drug-metabolizing enzyme activities or on the ultrastructural appearance of the liver. Increased hepatic OD activity was observed in the pregnant animal but no effect was observed in the lactating dam. Phenobarbitone received by the suckling rat had two distinct effects. Compared to control activities, twofold increases in hepatic OD activity were observed in rat pups as early as 4 days after birth, associated with a marked proliferation in hepatic smooth endoplasmic reticulum. In contrast, PB-related significant increases in neonatal hepatic CE and BSP–GSH conjugating enzyme activities were not observed until 21 days of age. In the 4-day-old treated pups, characteristic morphological changes included numerous small membrane whorls in addition to increased smooth endoplasmic reticulum and microbodies in the liver.

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