Curvilinear increase in methanol concentration after inhibition of oxidation by ethanol: significance for the investigation of endogenous methanol concentration and formation.

Endogenous methanol production was assessed over a period of 5 h in subjects given an infusion of ethanol to inhibit methanol oxidation in the liver after a period of fasting and abstinence from alcohol. Ethanol was administered to each of five subjects at rates of 0.35 g/kg per hour and 0.70 g/kg per hour. The rise in methanol concentration was biphasic regardless of the rate of ethanol administration, with a steeper gradient in the first 10-30 min. This may be due to the existence of a deep compartment from which methanol can be displaced by ethanol. This could take the form of loose binding of methanol to the hepatic oxidation enzymes as an enzyme-substrate complex, or a shift of the oxidation-reduction equilibrium between methanol and formaldehyde. The biphasic nature of the increase, with an initial steeper rise, means that the values obtained in the first 30 min should be excluded from the calculations when the rate of endogenous methanol production is determined by linear regression analysis. Endogenous methanol concentrations to be taken into account after ethanol administration are on average 0.4-0.6 mg/kg higher than those detectable in the absence of ethanol due to the additional method displaced from the deep compartment.