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Pharmacokinetics and metabolism of metioprim in pigs and goats

Pharmacokinetics and metabolism of metioprim in pigs and goats

Pharmacology & Toxicology 61(5): 330-334

The pharmacokinetics and metabolism of metioprim (MTP) have been studied after intravenous administration of a single dose of 5 mg/kg b.wt. to pigs (n = 4) and 10 mg/kg b.wt. to goats (n = 5). Kinetic parameters were calculated using a two-compartment open model. The elimination half-life was much shorter in goats (23 .+-. 4 min.) than in pigs (169 .+-. 17 min.). The apparent volume of distribution exceeded 1.0 l/kg b.wt. in both species indicating accumulation in tissues. Pigs excreted the major part of the dose (86 .+-. 9%) in urine and only a small part (9 .+-. 3%) in faeces, while the goats excreted almost equal amounts in urine (55 .+-. 5%) and faeces (38 .+-. 4%). Metabolism played the major role in elimination of MTP. Of the 80% of the dose excreted in urine within 24 hrs in pigs unchanged MTP made up 8%, metioprim sulfoxide 64% and O-desmethyl-MTP 8%. Metioprim sulfoxide was also the major metabolite in goats, but in this species another demethylated metabolite - metioprim sulfonic acid-was formed. Goats excreted 49 .+-. 7% of the dose in urine within 24 hrs of which unchanged MTP made up less than 1%, while metioprim sulfoxide accounted for about 35% and metioprim sulfonic acid for approximately 14%. Metabolites isolated from urine were identified by NMR-spectroscopy combined with EI, FAB or 252Cf plasma desorption mass spectrometry.

Accession: 001653481

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PMID: 3438229

DOI: 10.1111/j.1600-0773.1987.tb01830.x

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