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International Journal of Tropical Medicine
Year: 2008  |  Volume: 3  |  Issue: 2  |  Page No.: 30 - 35

Pharmacokinetic Evaluation of Drug Interactions Between Co-Trimoxazole and Zidovudine in Rabbits

C.S. Nworu, P.A. Akah, O.O. Ndu, A.C. Ezike and N.I. Onyekwelu    

Abstract: This study was conducted to determine the effects of concomitant administration of oral co-trimoxazole (120 mg kg 1) and zidovudine (30 mg kg 1) on their respective pharmacokinetics profiles in adult rabbits. The study was conducted in three phases, each separated from the other by a 2-week drug wash-out period. In the first phase, the animals received zidovudine (30 mg kg 1, p.o.) alone; in the second phase, they received co-trimoxazole (120 mg kg 1, p.o.) alone and in the third phase, both Zidovudine (30 mg kg 1, p.o.) and co-trimoxazole (120 mg kg 1, p.o.) were given concomitantly. Blood samples were withdrawn at intervals for 24 h and analysed for drug content. The concomitant administration of AZT and co-trimoxazole resulted in a non-significant (p>0.05) increase in peak plasma concentration, Area under Curve (AUC) and half-life (t1/2) of AZT and a decrease in the elimination rate constant, absorption rate constant, clearance and apparent volume of distribution of AZT. The peak plasma concentrations of zidovudine (876.9232.29 g mL 1), sulphamethoxazole (0.3490.007 g mL 1) and trimethoprim (0.6440.015 g mL 1) attained were increased non-significantly by 2.3, 9.17 and 5.59%, respectively. The apparent increase in serum concentration of co-trimoxazole, though not significant, resulted in a remarkable increase in the Reciprocal of Serum Inhibitory Titres (RSIT) against B. subtilis of up to 83.47% at the 2 h interval.The result of this study, suggests that co-trimoxazole does not cause major alterations in AZT pharmacokinetics in rabbits. In clinical practice, we could therefore infer that routine dosage adjustment may not be necessary when these 2 drugs are used concomitantly except in patients with co-existing hepatic or renal impairment where the risk of neutropaenia could be a major concern.

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