The effects of cobalt chloride, SKF-525A, and N-(3,5-dichlorophenyl)succinimide on in vivo hepatic mixed function oxidase activity as determined by single-sample plasma clearances.
1. Four drugs--antipyrine, theophylline, quinidine, and ethosuximide--were used as probes of in vivo hepatic mixed function oxidase (MFO) activity. Functional MFO activity was evaluated by estimating probe clearances subsequent to pretreatment of rats with either cobalt chloride, SKF-525A, or N-(3,5-dichlorophenyl) succiminide (NDPS). 2. Clearances of each probe were estimated from single plasma concentration measurements. Each pretreatment altered the clearances of this panel of probes in a different way. NDPS pretreatment increased theophylline clearance while slowing quinidine and ethosuximide clearances. SKF-525A slowed all probe clearances except for ethosuximide. Cobalt chloride slowed all probe clearances except for theophylline. 3. The use of multiple probes as substrates for the hepatic cytochrome P-450 system can provide some insight into the functional consequences of xenobiotic exposures on that system. Moreover, xenobiotic-induced functional changes on hepatic MFO when assessed in vivo appear to be modest relative to changes in in vitro activity or hepatic cytochrome P-450 content. This minimally invasive multiprobe method may be useful for assessing xenobiotic influences on human hepatic MFO in vivo.
Bachmann
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KA
Department of Pharmacology, University of Toledo College of Pharmacy, OH 43606.
Madhira
M S
MS
Rankin
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GO
D000818:Animals; D000983:Antipyrine / Q000097:blood / Q000493:pharmacokinetics; D003035:Cobalt / Q000494:pharmacology*; D005013:Ethosuximide / Q000097:blood / Q000493:pharmacokinetics; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D006899:Mixed Function Oxygenases / Q000378:metabolism*; D011335:Proadifen / Q000494:pharmacology*; D011802:Quinidine / Q000097:blood / Q000493:pharmacokinetics; D051381:Rats; D011919:Rats, Inbred Strains; D013388:Succinimides / Q000494:pharmacology*; D013806:Theophylline / Q000097:blood / Q000493:pharmacokinetics
D013388:Succinimides; C007352:N-(3,5-dichlorophenyl)succinimide; D003035:Cobalt; D005013:Ethosuximide; D011335:Proadifen; D013806:Theophylline; D006899:Mixed Function Oxygenases; C018021:cobaltous chloride; D011802:Quinidine; D000983:Antipyrine