Selective changes in oxidative xenobiotic metabolism in vivo and in vitro after parenteral administration of recombinant bovine somatotrophin to rats.
Effects of recombinant bovine somatotrophin (rBST) on in vivo and in vitro oxidative drug metabolism were studied in male rats. rBST was given subcutaneously at a dose of 250 or 500 micrograms 100 g-1 bodyweight 24 h-1 in different dosage patterns. Sulphadimidine (SDD) plasma clearance, urinary excretion of 6-hydroxy-SDD and the in vitro microsomal SDD-hydroxylations were only inhibited when rBST was given in three injections per 24 hours. The hepatic microsomal ethylmorphine N-demethylation rate and the testosterone hydroxylation rate at the 6 beta position were significantly reduced after one rBST injection per 24 hours. Microsomal testosterone hydroxylation rates at the 16 alpha and 2 alpha-positions were reduced depending on the frequency of rBST administration. It is concluded that the inhibition of in vivo and in vitro drug oxidation in rats by rBST is associated with selective changes in activity of cytochrome P450 enzymes in the liver.
Witkamp
R F
RF
Department of Veterinary Basic Sciences, University of Utrecht, The Netherlands.
Kolker
H J
HJ
Nijmeijer
S M
SM
Noordhoek
J
J
van Miert
A S
AS
D000284:Administration, Oral; D000818:Animals; D002417:Cattle; D005036:Ethylmorphine / Q000008:administration & dosage / Q000378:metabolism* / Q000493:pharmacokinetics; D005260:Female; D013006:Growth Hormone / Q000008:administration & dosage / Q000494:pharmacology*; D006207:Half-Life; D006900:Hydroxylation; D007279:Injections, Subcutaneous; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000494:pharmacology; D013418:Sulfamethazine / Q000008:administration & dosage / Q000378:metabolism* / Q000493:pharmacokinetics; D013739:Testosterone / Q000378:metabolism; D015262:Xenobiotics / Q000378:metabolism*
D011994:Recombinant Proteins; D015262:Xenobiotics; D013739:Testosterone; D013418:Sulfamethazine; D013006:Growth Hormone; D005036:Ethylmorphine