Biopharmaceutical aspects of the development of a sulfamethazine oral sustained release bolus for lambs

Pharmacokinetic parameters of sulfamethazine (SMZ) administered intravenously or orally either as an aqueous solution or as a lipid matrix formulation, were determined in young lambs. The value of the rate constant for elimination (ke) for the intravenous solution was 0.18 h−1 compared to 0.10 h−1 for the oral aqueous solution. The absolute bioavailability of the oral solution was about 75%. A lipid matrix containing 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 least 100 h provided that the mechanical strength of the bolus is sufficient. The pharmacokinetic data obtained with the lipid matrix show a release profile with two pulses due to both diffusion and erosion mechanisms. Plasma levels are maintained above the MIC of SMZ during 100 h with an absolute bioavailability of 51.7%