EFFECTS OF CO-TRIMOXAZOLE CO-ADMINISTRATION ON THE PHARMACOKINETICS OF AMODIAQUINE IN HEALTHY VOLUNTEERS
Journal Title: International Journal of Pharmacy and Pharmaceutical Sciences - Year 2015, Vol 7, Issue 9
Abstract
Objectives: Amodiaquine (AQ) is a 4-aminoquinoline antimalarial drug that is rapidly and extensively metabolized mainly by CYP2C8 enzyme to N-desethylamodiaquine (DEAQ). Co-trimoxazole (CTZ) is a combination (sulfamethoxazole and trimethoprim) antimicrobial agent with the trimethoprim component being a potent inhibitor of CYP2C8. AQ and CTZ are likely to be co-administered in the treatment of patients with malaria and susceptible bacterial infections. This study evaluates the effect of CTZ co-administration on the pharmacokinetics of AQ. Methods: In an open, two-way crossover study, 16 healthy volunteers were randomized to receive 600 mg single oral dose of AQ with or without the eleventh dose of CTZ (960 mg every 12 h for 7 days.) Blood samples were collected at pre-determined time intervals and analyzed for AQ and its major metabolite, DEAQ using a validated HPLC method.Results: Co-administration of AQ and CTZ resulted in significant increases in the total area under the concentration–time curve (AUCT), maximum plasma concentration (Cmax) and terminal elimination half-life (T½) of AQ compared with values with AQ dosing alone (AUCT:234.36±57.21 vs 366.42±62.48 h ng/ml; Cmax:24.86±7.28 vs 40.28±11.15 ng/ml; T½: 6.49±3.56 vs 9.24±2.97 h), while the oral plasma clearance markedly decreased (3862.66±756.38 vs 2654.28±650.12 L/h). Co-administration also led to a pronounced decrease in the ratio of AUC(metabolite)/AUC (unchanged drug) and highly significant decreases in Cmax and AUC of the metabolite.Conclusion: Study evaluated for the first time the effect of CTZ co-administration on the pharmacokinetics of AQ in healthy adult volunteers. CTZ significantly increased AQ exposure and decreased plasma levels of the active metabolite DEAQ.Â
Authors and Affiliations
Ademisoye Adebusuyi Akande, Soyinka Julius Olugbenga, Adegbola Jonathan Adebanjo, Abdullahi Sa’ad Toyin, Onyeji Cyprian Ogbona
Keywords
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