TY  - JOUR
T1  - Pharmacokinetic Evaluation of Drug Interactions Between Co-Trimoxazole and Zidovudine in Rabbits
AU - , C.S. Nworu AU - , P.A. Akah AU - , O.O. Ndu AU - , A.C. Ezike AU - , N.I. Onyekwelu 
JO  - International Journal of Tropical Medicine
VL  - 3
IS  - 2
SP  - 30
EP  - 35
PY  - 2008
DA  - 2001/08/19
SN  - 1816-3319
DO  - ijtmed.2008.30.35
UR  - https://makhillpublications.co/view-article.php?doi=ijtmed.2008.30.35
KW  - Acquired immunodeficiency syndrome
KW  -bioavailability
KW  -co-trimoxazole
KW  -HIV
KW  -pharmacokinetics
KW  -rabbits
KW  -zidovudine
AB  - This study was conducted to determine the effects of concomitant administration of oral co-trimoxazole (120 mg kg <SUP>1</SUP>) and zidovudine (30 mg kg <SUP>1</SUP>) 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 <SUP>1</SUP>, p.o.) alone; in the second phase, they received co-trimoxazole (120 mg kg <SUP>1</SUP>, p.o.) alone and in the third phase, both Zidovudine (30 mg kg <SUP>1</SUP>, p.o.) and co-trimoxazole  (120 mg kg <SUP>1</SUP>, 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 Blood samples were withdrawn at intervals  for 24 h and analysed for drug content.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&gt;0.05) increase in peak plasma concentration, Area under Curve (AUC) and half-life (t<SUB>1/2</SUB>) 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 (876.92±32.29 µg mL <SUP>1</SUP>), sulphamethoxazole  (0.349±0.007  µg  mL <SUP>1</SUP>)  and  trimethoprim (0.644±0.015 µg mL <SUP>1</SUP>) 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 <I> B.  subtilis</I>  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.
ER  -