Effects of phototherapy on the activity of microsomal mixed-function monooxygenases and the pharmacokinetics of [14C] hexobarbital in jaundiced and heterozygous Gunn rats.
We assessed the effects of in vivo phototherapy of Gunn rats on the activity of hepatic microsomal mixed-function monoxygenases and on the in vivo pharmacokinetics of [14C]HB. In experiment 1 no serial changes were seen in activities of hexobarbital hydroxylase or benzo(a)pyrene hydroxylase in hepatic microsomes isolated after 2, 4 or 7 days from homozygous jaundiced female Gunn rats exposed to continuous phototherapy or in matched Gunn rats maintained under dim light. In experiment 2 homozygous jaundiced (jj) and heterozygous nonjaundiced (Jj) Gunn rats of both sexes each received i.v. [14C]HB on 2 successive days. In random order, each was exposed on the first or second day to phototherapy for 5.5 hr, beginning 0.5 hr before the administration of HB; otherwise, each was kept under dim light. Plasma [14C]HB in arterial blood samples was separated chromatographically from its labeled metabolites, and biexponential plasma disappearance curves for [14C]HB were analyzed by a SAAM-23 computer program. Clearances in female rats were much slower. In both sexes, the total body clearance and volume of distribution of HB were decreased by 20% during phototherapy of the jj but not the Jj rats; terminal plasma half-life was unchanged. In experiment 3 direct in vitro illumination of [14C]HB did not cause photodegradation of this compound, despite the presence of albumin with or without bilirubin.
D000818:Animals; D001663:Bilirubin / Q000097:blood; D002250:Carbon Radioisotopes; D005260:Female; D006400:Hematocrit; D006579:Heterozygote; D006591:Hexobarbital / Q000378:metabolism*; D006720:Homozygote; D007565:Jaundice / Q000378:metabolism / Q000628:therapy*; D007567:Jaundice, Neonatal / Q000378:metabolism / Q000628:therapy; D007700:Kinetics; D008297:Male; D008862:Microsomes, Liver / Q000201:enzymology*; D006899:Mixed Function Oxygenases / Q000032:analysis*; D010789:Phototherapy; D051381:Rats; D011911:Rats, Gunn; D012737:Sex Factors
D002250:Carbon Radioisotopes; D006591:Hexobarbital; D006899:Mixed Function Oxygenases; D001663:Bilirubin