Abstract:
Background: Existence of anti-malarial generic drugs with low bioavailability marketed on sub-Saharan Africa raises
a concern on patients achieving therapeutic concentrations after intake of such products. This work compared
bioavailability of one generic tablet formulation with innovator’s product. Both were fixed dose combination tablet
formulations containing artemether and lumefantrine.
Methodology: The study was conducted in Dar Es Salaam, Tanzania, in which a survey of the most abundant
generic containing artemether-lumefantrine tablet formulation was carried out in retail pharmacies. The most
widely available generic (Artefan®, Ajanta Pharma Ltd, Maharashtra, India) was sampled for bioavailability
comparison with Coartem® (Novartis Pharma, Basel, Switzerland) - the innovator’s product. A randomized,
two-treatment cross-over study was conducted in 18 healthy Tanzanian black male volunteers. Each volunteer
received Artefan® (test) and Coartem® (as reference) formulation separated by 42 days of drug-free washout period.
Serial blood samples were collected up to 168 hours after oral administration of a single dose of each treatment.
Quantitation of lumefantrine plasma levels was done using HPLC with UV detection. Bioequivalence of the two
products was assessed in accordance with the US Food and Drug Authority (FDA) guidelines.
Results: The most widely available generic in pharmacies was Artefan® from India. All eighteen enrolled volunteers
completed the study and both test and reference tablet formulations were well tolerated. It was possible to
quantify lumefantrine alone, therefore, the pharmacokinetic parameters reported herein are for lumefantrine. The
geometric mean ratios for Cmax, AUC0-t and AUC0-∞ were 84% in all cases and within FDA recommended
bioequivalence limits of 80% – 125%, but the 90% confidence intervals were outside FDA recommended limits
(CI 49–143%, 53 - 137%, 52 - 135% respectively). There were no statistical significant differences between the two
formulations with regard to PK parameters (P > 0.05).
Conclusions: Although the ratios of AUCs and Cmax were within the acceptable FDA range, bioequivalence
between Artefan® and Coartem® tablet formulations was not demonstrated due to failure to comply with the FDA
90% confidence interval criteria. Based on the observed total drug exposure (AUCs), Artefan® is likely to produce a
similar therapeutic response as Coartem®
