Ketoconazole Artemether

Ketoconazole doubles the AUC of artemether and Iumefantrine, and other potent inhibitors of CYP3A4 are predicted to interact similarly. Although the clinical relevance of this is uncertain, the manufacturers of co-artemether currently advise against concurrent use. 

In one study, 16 healthy subjects were given ketoconazole 400 mg on day one then 200 mg daily for 4 days increased the AUC of artemether 2.4-fold, its metabolite dihydroartemisinin 1.7-fold and Iumefantrine 1.7-fold after a single dose of co-artemether 80/480 mg given with a high-fat breakfast. The maximum levels of the drugs were inereased to a similar extent. No ehanges in ECG parameters or increases in adverse events were noted. 

It was suggested that ketoconazole probably increases the levels of artemether and Iumefantrine via its effects on intestinal and/or hepatic cytochrome P450 isoenzyme CYP3A4. 

Lefevre G, Carpenter P, Souppart C, Schmidli H, McClean M, Stypinski D. Pharmacokinetics and electrocardiographic pharmacodynamics or artemether-lumefantrine (Riamet ) with concomitant administration of ketoconazole in healthy subjects, Br J Clin Pharmacol (2002) 54,... 

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