DETERMINATION OF THE PHARMACOKINETIC CHARACTERISTICS OF ETHANOL INFUSION SOLUTION AS AN ANTIDOTE IN METHANOL POISONING
Acute poisoning with alcohol and its surrogates occupies permanently high position in the Russian Federation’s statistics of poisoning. Therefore, it is a problem of social importance. Biochemical antagonism with methanol is shown by ethanol, so ethanol may be considered as an antidote in cases of acute methanol intoxication. However, ethanol has not been registered as a drug for the treatment of methanol poisoning in the Russian Federation. Production technology and standardization parameters for the 5% ethanol infusion solution in 5% glucose solution have been developed. The standardization of this document was carried out in accordance with the requirements of the State Pharmacopoeia of the XIV edition of the Russian Federation in accordance with the pharmacopeial monograph 1.4.1.0007.15 "Dosage forms for parenteral use" in terms of: description; visible mechanical inclusions; transparency; chromaticity; pH; qualitative analysis: for glucose - the reaction with Fehling's reagent, for ethanol - reaction of ethyl acetate formation; quantitative analysis: for glucose - refractometry, for ethanol - gas chromatography. The proposed analytical procedures have been validated. The procedure for the quantitative determination of methanol and ethanol in a biological fluid (urine) of laboratory animals by gas-liquid chromatography with flame ionization detection has been developed and validated for the purposes of pharmacokinetic studies. The alcohol content was calculated by the internal standard method according to the calibration graph. Determination of the pharmacokinetic characteristics of the 5% ethanol infusion solution in 5% glucose solution when administered together with methanol was held. On the model with subsequent administration with the infusion solution. It was shown that the area under the pharmacokinetic curve of methanol decreased approximately 2 times, the elimination rate constant increased 3 times, the half-life decreased 3 times, the volume of distribution decreased by almost 1.5 times, and the clearance increased by 2 times. The data obtained indicate a more rapid elimination of methanol from the organism after administration the infusion solution of ethanol, which makes it possible to consider a 5% ethanol solution in a 5% glucose solution as a promising antidote for methanol poisoning.