THE MODE OF ACTION OF DIETHYLCARBAMAZINE INVESTIGATED WITH ¹⁴C‐LABELLED DRUG

Abstract

Investigation of the metabolism and excretion of isotopically labelled diethylcarbamazine (Bangham, 1955) showed that this drug is rapidly metabolized and excreted in the urine after intravenous or oral administration. Ten to 15% of the dose is excreted as unchanged drug, 10-15% as diethylcarbamylpiperazine, 2-5% as methylpiperazine, and 1-6% as piperazine. The remainder of the dose-approximately 60%-is excreted as a compound which has been isolated in crude form but not yet identified.The present paper describes the distribution of the drug in the organs and tissues of the cotton rat (Sigmodon) and of the hooded rat (Rattus), the uptake of drug by microfilariae and adult worms, and the action of the drug on microfilariae in the first few minutes after intravenous injection. METHODS Estimation of RadioactivityThe methods for estimation of total radioactivity in solids and liquids, separation and estimation of individual metabolites, chromatography counting techniques and limits were as described by Bangham (1955). Microfilaria CountsThe cotton rats which were used weighed 150-300 g. and were reared in this Institute and infected here with Litomosoides carinii (Hawking and Sewell, 1948). Only animals with heavy infections were used.A blood sample was drawn into a calibrated 10 mm.' siliconed dry pipette, diluted by taking up a similar volume of 1% potassium citrate, and discharged on to a grease-free slide marked with two parallel lines 2 cm. apart. The pipette was rinsed again with about 10 mm.3 potassium citrate which was spread with the sample over the area-2 cm. X slide width (2.5 cm.). The slides were allowed to dry flat before being stained. Great care was needed during staining to avoid lifting and detachment of the edge of the film. Slides were usually stained with Giemsa, since this method was less likely to detach fragments from the film than staining with haemalum.

Equine onchocercal keratoconjunctivitis

“…In addition, dying microfilariae with typical inflammatory host responses are evident in tissues within 24 h of its administration, despite the fact that its metabolites accumulate very slowly in the tissues (Bangham 1955a, b). In view of this, it is likely that diethylcarbamazine potentiates the host's immune system and/or alters the microfilariae so that they are recognised and destroyed by the immune system (Hawking 1952;Bangham 1955b;Gibson et a1 1975 ;Schmidt et a1 1980). It has been hypothesised that a change in the surface structure of the microfilariae allows binding of host antibody and the triggering of the complement cascade with resultant chemotactic activity for inflammatory cells (Piessens and Beldekas 1979;Schmidt et a1 1980).…”

Antiparasite Chemotherapy

“…About 90% of the excreted drug is in the form of four different metabolites. The piperazine ring of the metabolites re mains intact but the side chains exhibit degradative changes (16,17 financial resources, to provide the necessary recurrent surveillance and drug administration. A promising solution to this problem is to 'achieve control by continuous DEC administration via medicated salt and other foods such as commercially prepared soups and orangeade.…”