Disposition of diethylcarbamazine in man and rat

Diethylcarbamazine and its major metabolite, diethylcarbamazine N-oxide have been identified and quantified in the urine of rats dosed orally with 14C-diethylcarbamazine citrate. The urinary excretion of diethylcarbamazine N-oxide as a percentage of dose was not dose-dependent. These observations are in agreement with previous studies. Carbon 14-diethylcarbamazine citrate (0.5 mg.kg-1) was administered orally to six patients under treatment for onchocerciasis. Blood samples were removed at timed intervals for 48 h and urine and faeces collected for 4 d. The urinary recovery of total radioactivity was 91-104% (mean=99.1%). Faecal recovery was 4-5% (mean=4.5%). The major component of the urinary radioactivity was diethylcarbamazine. Plasma and urinary concentrations of diethylcarbamazine and diethylcarbamazine N-oxide were measured by gas-liquid chromatography. Diethylcarbamazine was rapidly absorbed with a peak plasma concentration of 150-250 ng/ml attained in 2-3 h and eliminated with a half-life of 10-15 h. This elimination was, in distinction to the rat, by both renal and extra-renal routes with 40-62% excreted unchanged and 5-15% as the N-oxide. The clinical implications of these observations are discussed. As the metabolism of 14C-diethylcarbamazine differs greatly from man, the rat is unsuitable as an animal model in studies of diethylcarbamazine disposition. (author)