Effects of Artemisinin-Based Combination Therapies on Lipids and Hepatorenal Circulating Indices in Guinea Pigs

Abstract

Artemisinin-based Combination Therapies (ACTs) are employed as first-line agents in malaria chemotherapy. In many malaria endemic areas, ACTs are frequently abused partly due to resistance, poor drug control and inadequate health facilities. This study investigated the effects of prolong administration of Artesunate-Sulfadoxine-Pyrimethamine (ATS-SP), Artesunate-Amodiaquine (ATS-Amod) and Artemether-Lumefantrine (ATM-Lum) on plasma levels of biochemical parameters (AST, ALT, ALP, urea and creatinine) and lipids in guinea pigs. Adult guinea pigs were administered standard (NTD) or Double Therapeutic Dose (DTD) equivalents of ATS-SP, ATS-Amod or ATM-Lum for 14 days. Some other animals received similar drug treatments but were allowed to recover for 14 days. Control group was given vehicle. ATS-Amod caused significant (p<0.05) elevations in AST, ALT, urea and creatinine levels without altering ALP compared to control. The elevations were all reversed except the DTD-induced creatinine elevation. ATS-SP reversibly elevated (p<0.05) AST and creatinine levels. ATM-Lum caused no effect on urea, creatinine and ALT, but increased AST and ALP levels. Lipids were unaffected, except triglyceride level that was reversibly elevated (p<0.05) by ATS-SP (DTD). The results demonstrate that standard doses of the ACTs may have no harmful effects, but prolong overdose treatment with artesunate-amodiaquine or artesunate-SP may elevate creatinine and triglyceride levels, respectively.