A study of the pharmacokinetics and tissue residues of an oral trimethoprim/sulphadiazine formulation in healthy pigs.
Twenty-six healthy female pigs weighing 19.5-33 kg were used in three separate experiments. The animals were fed individually twice a day. Trimethoprim/sulphadiazine (TMP/SDZ) formulation was added to feed in the amount of 6 mg/kg bw (TMP) and 30 mg/kg bw (SDZ). TMP and SDZ concentrations in blood plasma, muscles, liver and kidneys were measured. Pharmacokinetic parameters show that the absorption of TMP from the alimentary tract in pigs is faster than the absorption of SDZ, and the elimination of TMP is slower than that of SDZ. The absorption half-lives were 0.96 (TMP) and 2.24 h (SDZ), whereas elimination half-lives were 5.49 (TMP) and 4.19 h (SDZ). The observed TMP:SDZ ratios in blood plasma after multiple dose administration ranged from 1:11.4 to 1:23.2. One day after administration of the last dose of TMP/SDZ the plasma concentration ratio was 1:15.5, but in muscles, liver and kidneys it was much lower: 1:0.79, 1:0.14 and 1:1.53 respectively. The absolute TMP and SDZ tissue concentrations 1 day after the last multiple dose administration were very low (maximum TMP: 0.29 micrograms/g in liver; maximum SDZ: 0.23 micrograms/g in kidneys). Neither drug was detected in any tissue 8 days after the last administration of TMP/SDZ. Based on our results, it was concluded that there is no support for the TMP:SDZ pharmaceutical ratio 1:5 in oral formulations of these compounds for pigs. The administration oral TMP/SDZ formulations once a day may result in the absolute tissue concentrations of these drugs being too low for antibacterial activity. The withdrawal period for such an oral TMP/SDZ formulation for pigs (according to accepted guidelines in Europe for MRL of TMP < 0.05 mg/kg of tissue) should not be less than 5 days.
Garwacki
S
S
Department of Pharmacology and Toxicology, Faculty of Veterinary Medicine, Warsaw Agricultural University, Poland.
Lewicki
J
J
Wiechetek
M
M
Grys
S
S
Rutkowski
J
J
Zaremba
M
M
D000284:Administration, Oral; D000818:Animals; D000890:Anti-Infective Agents / Q000008:administration & dosage / Q000097:blood / Q000378:metabolism / Q000493:pharmacokinetics*; D001682:Biological Availability; D002851:Chromatography, High Pressure Liquid / Q000662:veterinary; D004350:Drug Residues / Q000378:metabolism / Q000493:pharmacokinetics*; D004357:Drug Synergism; D005260:Female; D007668:Kidney / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D018482:Muscle, Skeletal / Q000378:metabolism; D012044:Regression Analysis; D013411:Sulfadiazine / Q000008:administration & dosage / Q000097:blood / Q000378:metabolism / Q000493:pharmacokinetics*; D013552:Swine; D014018:Tissue Distribution; D014295:Trimethoprim / Q000008:administration & dosage / Q000097:blood / Q000378:metabolism / Q000493:pharmacokinetics*
D000890:Anti-Infective Agents; D013411:Sulfadiazine; D014295:Trimethoprim