Comparison of bioavailability between the most available generic tablet formulation containing artemether and lumefantrine on the Tanzanian market and the innovator’s product

Malaria Journal

Research

Philip Sasi¹  Omar Juma²  Mwajuma Chemba²  Mastidia Rutaihwa²  Salim Abdulla²  Seif Shekalaghe²  Omary MS Minzi³  Eliford Ngaimisi³  Ignace A Marealle³ 

[1] Department of Clinical Pharmacology, School of Medicine, Muhimbili University of Health and Allied Sciences, PO BOX 65010, Dar Es Salaam, Tanzania;Ifakara Health Institute, PO Box 78373, Dar es Salaam, Tanzania;Unit of Pharmacology and Therapeutics, School of Pharmacy, Muhimbili University of Health and Allied Sciences, PO BOX 65013, Dar Es Salaam, Tanzania;

关键词: Bioavailability;    Bioequivalence;    Artefan;    Coartem;    Generics;   

DOI  :  10.1186/1475-2875-12-174

 received in 2013-03-13, accepted in 2013-05-15,  发布年份 2013

来源: Springer

【 摘 要 】

BackgroundExistence 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.MethodologyThe 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.ResultsThe 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).ConclusionsAlthough 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®.

【 授权许可】

CC BY   
© Minzi et al.; licensee BioMed Central Ltd. 2013