Safety Profile of Concomitant Administration of Artemisinin Based Therapy and Calcium Compounds in Laboratory Animals

Abstract

Artemisinin based combination therapy (ACT) specifically artemisinin-lumefantrine recommended for human malaria treatment may be prescribed for patients who are on calcium supplements unknowingly. The interaction of the two and end result on body metabolic and physiological process is not known. There is need to assess the safety and possible adverse effects of separate and combined administration of these agents. Randomized groups of experimental and control rats were used to evaluate the interaction of the two. Two of the groups of rats were placed on calcium supplement for one month after which ACT was orally administered to one of the group for 3-6 days. Another group of rats not on calcium supplement was administered with ACT only. The control group of rats was administered with sterile distilled water and kept at same laboratory conditions as experimental groups. Levels of Na+, Ca2+, K+, creatinine and urea were analyzed in plasma of all groups of rats. Concomitant use of artemisinin-lumefantrine and calcium supplement induced significant elevation of plasma Na+, Ca2+ and creatinine concentrations. Extended and possibly repeated use of ACT alone raised the plasma Na+ and creatinine level above the normal value after the first three days. It was concluded that repeated and or prolonged use of artemisinin-lumefantrine alone and in combination with calcium lead to renal dysfunction in laboratory animals. Our findings highlight areas that require clarification by long term studies and provide a basis for further research and recommend that related studies be carried out in human subjects for comparison with these findings