Pharmacokinetics and Metabolism of Metioprim in Pigs and Goats

Abstract

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 1/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.

Metabolism and Disposition of Aditoprim in Swine, Broilers, Carp and Rats

“…This observation indicated that ADP had a good absorption profile in these species. The excretion pathway was similar to its analogs TMP and metioprim, with 66–85% of the dose recovered in the urine after the oral administration 21 22 . In contrast to the excretion of TMP in rats, more than 95% of the oral dose was recovered within 3 d. ADP showed a relatively slow elimination trend (approximately 84% of the oral dose during 0–3 d) in comparison with the rat excreta, implying that ADP would have a longer elimination half-life than TMP in the organism.…”

Metabolism and Tissue Elimination of Diaveridine in Swine, Chickens, and Rats Using Radioactive Tracing Coupled with LC–ESI–IT–TOF/MS

“…Similar to DVD analogues TMP, metioprim, and aditoprim (ADP), about 66∼85% of the oral ingestion dosage was excreted via urine. This finding demonstrates the high bioavailability of 2,4-diaminopyrimidine medicines, with renal excretion serving as their primary route of elimination. − DVD is used as a classical antiprotozoal agent; however, its good absorption implies that it also has a good curative effect as an antibacterial synergist for treating systemic infection. Chickens excreted DVD-related metabolites more quickly than swine and rats, with a 91.1% recovery of the dose during 2 d compared with 84.0% for swine, 80.3% for female rats, and 81.7% for male rats.…”

“…The results were consistent with those shown with the structural analogues TMP, brodimoprim, and metioprim. 28,29,33,34 M0, M1, and M2 were consistent metabolites for the three tested species. M2 was found in the plasma and bile in chickens but not in the excreta.…”

“…The results of our research showed that O -demethylation, α-hydroxylation, and phase II conjugative metabolism are all involved in the biotransformation of DVD. The results were consistent with those shown with the structural analogues TMP, brodimoprim, and metioprim. ,,, M0, M1, and M2 were consistent metabolites for the three tested species. M2 was found in the plasma and bile in chickens but not in the excreta.…”