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, T rimethoprim/sulphadiazine (TMP/SDZ) formulation was added to feed in t he amount of 6 mg/kg bw (TMP) and 30 mg/kg bw (SDZ), TMP and SDZ conce ntrations in blood plasma, muscles, liver and kidneys were measured, P harmacokinetic parameters show that the absorption of TMP from the ali mentary tract in pigs is faster than the absorption of SDZ, and the el imination 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 TMF:SDZ ratios in blood pla sma after multiple dose administration ranged from 1:11.4 to 1:23.2. O ne day after administration of the last dose of TMP/SDZ the plasma con centration 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 a nd SDZ tissue concentrations 1 day after the last multiple dose admini stration were very low (maximum TMP: 0.29 mu g/g in liver; maximum SDZ : 0.23 mu g/g in kidneys), Neither drug was detected in any tissue 8 d ays 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 admin istration of oral TMP/SDZ formulations once a day may result in the ab solute tissue concentrations of these drugs being too low for antibact erial activity, The withdrawal period for such an oral TMP/SDZ formula tion for pigs (according to accepted guidelines in Europe for MRL of T MP < 0.05 mg/kg of tissue) should not be less than 5 days.