A comparison of pharmacokinetics of two tablet formulations containing artemether / lumefantrine – quality criteria for malaria treatment assurance

Abstract

Background: Treatment of non-severe malaria remains a challenge to endemic areas including Tanzania. Since November 2006, Coartem® an artemisinin based combination therapy (ACT) containing artemether-lumefantrine (ALu), replaced sulphadoxine/pyrimethamine (SP) as first line drug for treatment of uncomplicated malaria in Tanzania because of emergence and spread of SP resistance to Plasmodium falciparum. Currently a number of generic artemether-lumefantrine drugs are available in resource limited settings such as Tanzania and yet few pharmacokinetics (PK) and bioequivalence (BE) data in these populations are available. Considering the liability to substandard manufacturing, there is a need to assess quality of generic ALu tablet formulations. Objective: We assessed the quality of the most prevalent generic artemether-lumefantrine tablet formulation available in the Tanzanian market using clinical study for bioequivalence. Methodology: Survey of available generics of artemether-lumefantrine tablet formulations was carried out in retail pharmacies in Dar es Salaam in which the most widely available generic was sampled (Artefan® from India) for quality assessment. The randomized, 2-treatment cross over study was conducted in 18 healthy Tanzanian male volunteers. Each volunteer received Artefan® (test) and Coartem® (reference) formulation under fed condition separated by 42 days of drug-free washout period. Serial blood samples were obtained over 168 hours after oral administration of each treatment. Quantitation of lumefantrine plasma levels was done using HPLC with UV detection. Formulation lumefantrine bioequivalence was assessed in accordance with the US Food and Drug Authority (FDA) bioequivalence criteria. Results: All eighteen enrolled volunteers completed the study and both test and reference drug formulations were well tolerated. The mean ± SD for lumefantrine primary PK parameters for bioequivalence Cmax, Tmax, AUC0-t and AUC0-∞ under fed condition for artefan.