Abstract
The pharmacokinetic of deflazacort after intravenous and oral administration and the effect of erythromycin on the disposition of deflazacort in rabbits were investigated. A parallel study was carried out in twelve rabbits. The plasma concentration-time profiles of deflazacort were determined after intravenous and oral administration of single dosages of 5mg/kg in the presence and absence (baseline) of multiple dose erythromycin regimens. Plasma concentrations of 21-desacetyldeflazacort were determined by HPLC. Plasma concentration-time curves were analysed by compartmental pharmacokinetic and noncompartmental methods. The t½λz values following intravenous and oral administration were 3.67 and 4.96hr, respectively. The apparent volume of distribution at steady-state (Vss ) was 4.08±0.31L/kg, this value indicates that deflazacort is widely distributed into the extravascular tissues. Moreover, bioavailability after oral administration of deflazacort (F=87.48%) was high. Pharmacokinetic analysis after both routes of administration revealed a significant reduction in total body clearance, a significant increase in mean residence time, half-life and plasma concentrations of the steroid in the presence of multiple dose erythromycin. The results indicated the influence of the erythromycin on deflazacort disposition, which is consistent with a pharmacokinetic-type interaction in the elimination of the drug from the body. Moreover, this interaction should be considered to avoid adverse effects when using both drugs concomitantly.
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