Evaluation of pharmacokinetic and bioequivalence of brands of sulphadoxine-pyrimethamine tablets used in intermittent preventive therapy for pregnant women in Nigeria

Abstract

Objectives: The aim of this study is to investigate the pharmacokinetic and relative bioavailability of three tablet formulation containing sulphadoxine pyrimethamine (SP) used for intermittent preventive therapy in pregnant women in Nigeria to see whether there is need for dose adjustment. Methods: Twelve healthy volunteers(pregnant women at their fourth month of pregnancy) attending antenatal clinic (ANC)were randomised to receive a single oral dose of three SP tablets each containing 500mg sulphadoxine (XD)and 25mg pyrimethamine (PY) in form of A (innovator product) and B,C(locally manufactured SP tablet formulation),after an overnight fasting. Several blood samples (100μl) were collected from a finger prick in duplicates up to ten days and dried on a Whatman® filter paper. The samples were analysed for DX and PY using the High Performance Liquid Chromatography (HPLC) method. The pharmacokinetic parameters assessed were maximum plasma concentration (Cmax), area under curve (AUC), elimination half life (t1/2), time to attain maximum concentration (tmax) and relative bioavailability using the single compartment model. Results: Sample formulation B was significantly lower than samples A and C (p<0.1) in mean plasma concentration (Cmax), area under curve (AUC). Conclusion: The difference shows in vivo inequivalence between the products, and calls for caution in using these products, however the pharmacokinetic results shows that there is no need for dose adjustment of SP in pregnancy since they attain therapeutic concentration in vivo, indicating that their kinetics is not altered in pregnancy.