Absorption, distribution and excretion of artemether in mice and rats

Artemether, methyl-dihydro-artemisinine, is a much more potent antimalarial than artpmiSJnine. In this paper, the absorption, distribution, excretion and demethylation of artemether in mice and rats are reported. Thirty minutes after iv in mice. a high level of radioactivities was found in liver, adrenals arid kidneys, while appreciable radioactivities were present in spleen. lungs, small intestine. heart. femurs. muscle. stomach and large intestine. The radioactivities in testis and brain were low. The radioactivities in whole blood. plasma and bile were very high. The pattern of distribution of [3H]artemether in rats was similar to that in mice. except a higher radioactivity in the lungs of rats. The drug was rapidly taken up by various organs. Only very low level of activity was detected in the tissues 24 h after iv [3H]artemether. Following iv [3ll]artemether in mice. the total radioactivity was found to be 41. 3% in urine and 26.9% in feces within 24-h. and 56.0% in urine and 39.Ogto in feces within 72 h. Biliary excretion was also considerable. In rats with a biliary cannula. 32.o% of an iv dose of [3H]artemether was recovered from the bile collected for 3 h. The amount of demethylation of artemether (etheric methyl) in 24 h after iv or im in mice was found to be 31.3% and 14 . 9%. respectively. and the degree of demethylation under the induction of phenobarbital was increased markedly (P