BIOPHARMACEUTICAL ASPECTS OF THE DEVELOPMENT OF A SULFAMETHAZINE ORALSUSTAINED-RELEASE BOLUS FOR LAMBS

Pharmacokinetic parameters of sulfamethazine (SMZ) administered intrav enously or orally either as an aqueous solution or as a lipid matrix f ormulation, were determined in young lambs. The value of the rate cons tant for elimination (k(e)) for the intravenous solution was 0.18 h(-1 ) compared to 0.10 h(-1) for the oral aqueous solution. The absolute b ioavailability of the oral solution was about 75%. A lipid matrix cont aining SMZ and a high density excipient is able to be retained in the reticulo-rumen and to produce a sustained release of the drug for at l east 100 h provided that the mechanical strength of the bolus is suffi cient. The pharmacokinetic data obtained with the lipid matrix show a release profile with two pulses due to both diffusion and erosion mech anisms, Plasma levels are maintained above the MIC of SMZ during 100 h with an absolute bioavailability of 51.7%.