Pharmacokinetics Of Artemether-Lumefantrine Combination Therapy In Malaria Chemotherapy
Objectives: The therapeutic effects of artemether monotherapy compared to artemether-lumefantrine combined therapy in malaria based on their pharmacokinetic parameters such as absorption, elimination constants, area under the curve, bioavailability, volume of distribution and half-lives were investigated. Methods: Design was by single blind technique at Our Lady of Lourdes Hospital, Ihiala, Anambra State, Nigeria. Presence and concentration of Plasmodium falciparum in the patients' blood were confirmed by microscopy. Analysis of blood samples for drug. Concentration was by high performance liquid chromatography (hplc). Results: Results showed that peak serum concentration (Cmax) was 12.22±0.11µg for monotherapy and 82±0.8µg for combination therapy Area under the curve (AUC) was 756±0.11µ h-1ml-1for monotherapy and 415±0.11µh-1ml-1 for combination therapy. Apparent volume of distribution (Vd) was 317±0.5ml for monotherapy and 23±0.1ml for combination therapy. Bioavailability (f) was 0.4±0.00 for monotherapy and 0.12±0.00 for combination therapy. Absorption rate constant (Ka) was 18±0.11 h-1 for monotherapy and 15±0.11 h-1 for combination therapy. Elimination rate constant (Kel) was 0.33±0.00 h-1 for monotherapy and 0.29±0.00 h-1 for combination therapy, since elimination constant calculates half-lives of the drugs. Conclusion: Results indicate significant differences between the pharmacokinetic parameters employed, particularly of artemether (2.1±0.03) as control with short elimination half-life and artemether – lumefartrine (2.3±0.01h-1) with longer elimination half-life. These significant variations might be attributed to the enhanced effect of the combined drugs possibly due to synergistic effect.
Keywords: Pharmacokinetics, Artemether, Lumefantrine, Monotherapy, combination therapy, Plasmodium falciparum.
Tropical Journal of Medical Research Vol. 12 (1) 2008: pp. 9-13