Oral bioavailability of sulphonamides in ruminants: A comparison between sulphamethoxazole, sulphatroxazole, and sulphamerazine, using the dwarf goat as animal model
| Autor: | Renger F. Witkamp, R.F.M. Maas, G. Semjén, V. Ratz, A.S.P.J.A.M. van Miert |
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| Předmět: |
Male
Time Factors Sulfamethoxazole Sulphamerazine Administration Oral Biological Availability Absorption (skin) Pharmacology Biology Sulfamerazine Rumen chemistry.chemical_compound Pharmacokinetics medicine Animals Cross-Over Studies General Veterinary Goats Ruminants Crossover study Trimethoprim Bioavailability Diaminopyrimidine chemistry Injections Intravenous medicine.drug |
| Zdroj: | Scopus-Elsevier |
| Popis: | 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 tmax +/- SD : 0.8 +/- 0.2h). However, the drug was rapidly eliminated from the plasma (t1/2 beta : 2.4 +/- 1.5 h) 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/l) 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. |
| Databáze: | OpenAIRE |
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