EFFECTS OF DIETHYLDITHIOCARBAMATE, A METABOLITE OF DISULFIRAM, ON THE PHARMACOKINETICS OF ALCOHOL AND ACETALDEHYDE IN THE RAT

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The effects of diethyldithiocarbamate (DDC), a metabolite of disulfiram which is known as Antabuse, on the blood concentrations of alcohol and acetaldehyde were determined simultaneously by head space gas chromatography in rats. After an intravenous injection of alcohol, the blood concentration of acetaldehyde was much lower than that of the alcohol. A pharmacokinetic model featuring the liver compartment for acetaldehyde was used to estimate pharmacokinetic parameters on the assumption that the distribution volumes of the central compartments were same for alcohol and acetaldehyde, and that the elimination rate of acetaldehyde from liver was large enough to isolate the liver compartment from the central compartment. The results showed that the clearance of alcohol was 0.0226 l/min/kg and the elimination rate constant of acetaldehyde from the liver compartment was very large and 35 min^<-1>. The administration of DDC decreased the above significantly to 0.0132 l/min/kg and 20 min^<-1>, respectively. After intravenous infusion of acetaldehyde, the time course of the blood concentration of acetaldehyde was analyzed by the one compartment model. The estimated elimination rate constants from blood and the distribution volume were in good agreement with those calculated from blood and the distribution volume were in good agreement with those calculated from alcohol injection, indicating the appropriateness of the method used in this study. DDC had no effect on the elimination of infused acetaldehyde from blood indicating that the elimination may be due to the loss from lungs into breath, from skin surfaces and/or from the kidney but not by metabolism in the liver.
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EFFECTS OF DIETHYLDITHIOCARBAMATE, A METABOLITE OF DISULFIRAM, ON THE PHARMACOKINETICS OF ALCOHOL AND ACETALDEHYDE IN THE RAT

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