Acetaminophen metabolism in vivo by pregnant, fetal, and neonatal guinea pigs.
Acetaminophen (50 mg/kg body weight) was administered by iv injection to pregnant guinea pigs (60-65 days of gestation) and by ip injection to cesarean-derived term (67 days of gestation) pups. At suitable time intervals after treatment, the concentrations of drug, glucuronide (GLU), and sulfate (SO4) in blood plasma, urine, and bile were measured by high-performance liquid chromatography (HPLC). At 60-65 days of gestation, guinea pig fetuses formed both GLU and SO4, an approximate ratio of 2:1 being observed with mean concentrations of the order of 43 and 27 micrograms/mL being measured for GLU and SO4, respectively at 180 min post-treatment. At the same time interval, the major detoxification product found in the blood plasma of the pregnant dams was GLU (104 micrograms/mL) with only minute amounts (4.2 micrograms/mL) of SO4 being detected. In cesarean-derived and acetaminophen-treated pups, euthanized at 2 or 4 hr post-treatment, plasma levels of GLU were approximately twofold higher relative to the concentration of SO4 at both time intervals. Significant differences were not observed in either bile or urine at 2 hr post-treatment but by 4 hr after treatment the levels of GLU found in the bile and urine were two- or threefold higher than those of SO4. In contrast to the adult guinea pig where GLU forms some 90% of the urinary excretory product and SO4 accounts for only 7%, the SO4 pathway of detoxification appears to be of significant importance to the fetal and neonatal animal.
Ecobichon
D J
DJ
Department of Pharmacology and Therapeutics, McGill University, Faculty of Medicine, Montreal, Quebec, Canada.
Hidvegi
S
S
Comeau
A M
AM
Varma
D R
DR
D000082:Acetaminophen / Q000031:analogs & derivatives / Q000378:metabolism / Q000493:pharmacokinetics*; D000818:Animals; D000831:Animals, Newborn / Q000378:metabolism*; D001711:Biotransformation / Q000502:physiology; D005260:Female; D005333:Fetus / Q000378:metabolism*; D006168:Guinea Pigs; D011247:Pregnancy; D011270:Pregnancy, Animal / Q000378:metabolism*
D000082:Acetaminophen; C037386:acetaminophen glucuronide; C045667:acetaminophen sulfate ester