title: Pharmacokinetics of sulfadimethoxine and sulfamethoxazole in combination with trimethoprim after oral single- and multiple-dose administration to healthy pigs.
abstract: The pharmacokinetics were studied of sulfadimethoxine (SDM) or sulfamethoxazole (SMX) in combination with trimethoprim (TMP) administered as a single oral dose (25 mg + 5 mg per kg body weight) to two groups of 6 healthy pigs. The elimination half-lives of SMX and TMP were quite similar (2-3 h); SDM had a relatively long half-life of 13 h. Both sulfonamides (S) were exclusively metabolized to N4-acetyl derivatives but to different extents. The main metabolic pathway for TMP was O-demethylation and subsequent conjugation. In addition, the plasma concentrations of these drugs and their main metabolites after medication with different in-feed concentrations were determined. The drug (S:TMP) concentrations in the feed were 250:50, 500:100, and 1000:200 mg per kg. Steady-state concentrations were achieved within 48 h of feed medication, twice daily (SDM+TMP) or three times a day (SMX+TMP). Protein binding of SDM and its metabolite was high (>93%), whereas SMX, TMP and their metabolites showed moderate binding (48-75%). Feed medication with 500 ppm sulfonamide combined with 100 ppm TMP provided minimum steady-state plasma concentrations (C(ss,min)) higher than the concentration required for inhibition of the growth of 90% of Actinobacillus pleuropneumoniae strains (n = 20).
authors.affiliation: State Institute for Quality Control of Agricultural Products, Department of Toxicology, Wageningen, The Netherlands.
authors.forename: M J
authors.initials: MJ
authors.lastname: Mengelers
authors.forename: E R
authors.initials: ER
authors.lastname: van Gogh
authors.forename: M B
authors.initials: MB
authors.lastname: Huveneers
authors.forename: P E
authors.initials: PE
authors.lastname: Hougee
authors.forename: H A
authors.initials: HA
authors.lastname: Kuiper
authors.forename: A
authors.initials: A
authors.lastname: Pijpers
authors.forename: J H
authors.initials: JH
authors.lastname: Verheijden
authors.forename: A S
authors.initials: AS
authors.lastname: van Miert
mesh_terms: D000284:Administration, Oral; D000821:Animal Feed; D000818:Animals; D000890:Anti-Infective Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D019540:Area Under Curve; D004338:Drug Combinations; D006207:Half-Life; D008297:Male; D013412:Sulfadimethoxine / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D013552:Swine / Q000378:metabolism*; D015662:Trimethoprim, Sulfamethoxazole Drug Combination / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*
chemical_list: D000890:Anti-Infective Agents; D004338:Drug Combinations; D013412:Sulfadimethoxine; D015662:Trimethoprim, Sulfamethoxazole Drug Combination