ORAL BIOAVAILABILITY OF SULFONAMIDES IN RUMINANTS - A COMPARISON BETWEEN SULFAMETHOXAZOLE, SULPHATROXAZOLE, AND SULFAMERAZINE, USING THE DWARF GOAT AS ANIMAL-MODEL

The various sulphonamides show marked differences in disposition chara cteristics after administration to ruminants, For use in combination w ith a diaminopyrimidine derivative such as trimethoprim or baquiloprim , it is essential that a sulphonamide has similar pharmacokinetic prop erties in order to obtain optimal synergy, In the present study the ph armacokinetics of sulphamethoxazole, sulphatroxazole, and sulphamerazi ne were investigated in dwarf goats (n=6) after IV and intraruminal ad ministration at a dose of 30 mg/kg bodyweight, In addition, the in vit ro binding of sulphamerazine to ruminal contents was studied as a poss ible explanation for a reduced absorption rate, Sulphamethoxazole show ed the most rapid absorption after intraruminal administration (mean t (max) +/- SD : 0.8 +/- 0.2h). However, the drug was rapidly eliminated from the plasma (t(1/2 beta) : 2.4 +/- 1.5h) and the bioavailability was only 12.4 +/- 4.7%, most likely due to an extensive 'first-pass' e ffect, The bioavailability of orally administered sulphamerazine and s ulphatroxazole was much higher (67.6 +/- 13.5 % and 70.2 +/- 32.3 %, r espectively), After intraruminal administration, sulphatroxazole showe d the highest plasma peak concentration (26.1 +/- 6.3 mg/l) and the lo ngest plasma half-life (4.7 +/- 1.8h) and mean residence time (13.9 +/ - 4.5 h), Sulphamerazine showed considerable binding to rumen contents iii vitro, Based on its pharmacokinetic properties sulphatroxazole ap pears to be a suitable candidate to be used in combination with the mo re recently developed diaminopyrimidines such as baquiloprim.