Oral bioavailability of sulphonamides in ruminants: A comparison between sulphamethoxazole,sulphatroxazole, and sulphamerazine,using the dwarf goat as animal model

Summary

The various sulphonamides show marked differences in disposition characteristics after administration to ruminants. For use in combination with a diaminopyrimidine derivative such as trimethoprim or baquiloprim, it is essential that a sulphonamide has similar pharmacokinetic properties in order to obtain optimal synergy. In the present study the pharmacokinetics of sulphamethoxazole, sulphatroxazole, and sulphamerazine were investigated in dwarf goats (n=6) after IV and intraruminal administration at a dose of 30 mg/kg bodyweight. In addition, the in vitro binding of sulphamerazine to ruminal contents was studied as a possible explanation for a reduced absorption rate. Sulphamethoxazole showed 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_1/2ß : 2.4 ± 1.5h) and the bioavailability was only 12.4 ± 4.7 %, most likely due to an extensive ‘first‐pass’ effect. The bioavailability of orally administered sulphamerazine and sulphatroxazole was much higher (67.6 ± 13.5 % and 70.2 ± 32.3 %, respectively). After intraruminal administration, sulphatroxazole showed the highest plasma peak concentration (26.1 ± 6.3 mg/I) and the longest plasma half‐life (4.7 ± 1.8h) and mean residence time (13.9 ± 4.5 h). Sulphamerazine showed considerable binding to rumen contents in vitro. Based on its pharmacokinetic properties sulphatroxazole appears to be a suitable candidate to be used in combination with the more recently developed diaminopyrimidines such as baquiloprim.