A COMPARATIVE-STUDY OF THE PHARMACOKINETICS OF INTRAVENOUS AND ORAL TRIMETHOPRIM SULFADIAZINE FORMULATIONS IN THE HORSE

The biopharmaceutical properties of four fixed trimethoprim/sulfonamid e combinations were investigated in the horse. Eight fasted horses wer e dosed at 1 week intervals in a sequentially designed study with one intravenous (i.v.) and three oral trimethoprim/sulfadiazine (TMP/SDZ) formulations (1, 2 and 3) administered at a dose of 5 mg/kg trimethopr im (TMP) and 25 mg/kg sulfadiazine (SDZ). Plasma concentrations of eac h compound were monitored for 48 h. Pharmacokinetic parameters (volume of distribution, bioavailability and total body clearance) for TMP an d SDZ were calculated and compared. After oral administration plasma c oncentrations of TMP and SDZ increased rapidly. With all three paste f ormulations, TMP peak plasma concentrations were attained within 2 h. SDZ mean peak plasma concentrations were reached at 2.59 +/- 0.48 h fo r a commercial paste (1), and at 1.84 +/- 0.66 h and 1.95 +/- 0.61 h f or the two self-made formulations (2 and 3). Mean peak plasma TMP conc entrations (+/- SD) were 1.72 +/- 0.36 mu g/ml, 1.42 +/- 0.37 mu g/ml and 1.31 +/- 0.36 mu g/ml, and mean peak plasma SDZ concentrations 12. 11 +/- 4.55 mu g/ml, 12.72 +/- 3.47 mu g/ml and 15.45 +/- 4.74 mu g/ml for preparations 1, 2 and 3. The bioavailability of TMP was 67.0 +/- 20.3%, 57.7 +/- 21.6% and 60.9 +/- 18.9% and of SDZ 57.6 +/- 14.8%, 59 .3 +/- 19.5% and 65.9 +/- 5.8% for SDZ for 1, 2 and 3, respectively. F ollowing i.v. administration TMP/SDZ plasma concentration ratios appro ached the optimal 1:20 ratio (+/-10%) for about 5 h, but following the oral administrations this ratio was only achieved far a very short ti me-span. No adverse effects were seen following i.v. and oral administ ration. In considering the pharmacokinetic data in combination with in vitro antibacterial sensitivity data, it is concluded that treatment at a dose of 5 mg/kg TMP and 25 mg/kg SDZ with a dosing interval of 12 h can be regarded as therapeutically effective for susceptible bacter ia (MIC(90) 0.25/4.75) for all three oral formulations. It is conclude d that neither the formulation nor the addition of different excipient s result in significantly different bioavailabilities.