Glucuronide cleavage

Artemisinin is a natural endoperoxide-containing sesquiterpene, isolated from a plant used in traditional Chinese medicine. Acetalic artemisinin derivatives (arte-mether, artesunate) are very active against chemo-resistant forms of Plasmodium falciparum, and are clinically used for the treatment. However, they suffer from an unfavourable pharmacological profile. They are quickly metabolised by fast oxidative metabolism, hydrolytic cleavage and glucuronidation. 

N-sulfonation N-Glucuronidation, hydroxylation, N-oxidation, ring cleavage, oxidation... 

Animals. 98.5-100% of 14C was excreted within 7 days. The major metabolic routes were deethylation of the 4-ethoxy group, cleavage of the carbamate linkage, acetylation, and finally formation of the glucuronide and sulfate conjugates... 

Disposition in the Body. Readily absorbed after oral administration bioavailability almost 100%. Metabolised by demethylation and subsequent deamination to the active metabolites desme-thylchlordiazepoxide and demoxepam. Demoxepam is further metabolised by hydrolysis with cleavage of the lactam ring and by reduction to desmethyldiazepam (nordazepam) followed by hydroxylation to oxazepam (desmethyldiazepam and oxazepam are also pharmacologically active). About 60% of a dose is excreted in the urine and 10 to 20% is eliminated in the faeces less than 1% of a dose is excreted in the urine unchanged, about 6% is excreted as demoxepam, and the remainder as ring-opened derivatives and glucuronide conjugates of oxazepam and other hydroxylated metabolites. 

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