Pharmacokinetic and deuterium isotope effect studies on the metabolism of formaldehyde and formate to carbon dioxide in rats in vivo.
The effect of deuterium substitution on the metabolism of formaldehyde and formate to carbon dioxide in vivo was examined. Four groups of male Sprague-Dawley rats were injected ip with carbon-14-labeled formaldehyde, formaldehyde-d2, sodium formate, or sodium formate-d at doses of 0.67 mmol/kg. Similar rates of labeled carbon dioxide exhalation were observed for the four groups of animals, the cumulative excretion of 14CO2 in breath reaching 68-71% of the theoretical value 12 hr after injection in all cases. Plots of amount remaining to be excreted showed that the metabolism was biexponential, with half-lives of approximately 0.4 and 3 hr for the two phases for each of the four compounds. Competitive experiments in which equimolar mixtures of CH2O with CD2O or HCO2- with DCO2- were injected also failed to reveal a substantial isotope effect, although the cumulative conversion of formate to carbon dioxide was significantly higher than that of its deuterated analog at four time points in the middle of the 8-hr mixed-isotope experiment. The data indicate that deuterium substitution has little or no effect on the rates and extents of in vivo oxidation of these 1-carbon species to carbon dioxide, although a small decrease of up to 10% in reactivity under the conditions employed cannot be excluded. The results support the use of carbon dioxide exhalation data in the measurement of deuterium isotope effects on oxidative demethylation reactions such as those that occur in the activation of the carcinogen, N-nitrosodimethylamine.
D000818:Animals; D002245:Carbon Dioxide / Q000378:metabolism*; D002250:Carbon Radioisotopes; D003903:Deuterium / Q000378:metabolism*; D004128:Dimethylnitrosamine / Q000378:metabolism; D005557:Formaldehyde / Q000378:metabolism*; D005561:Formates / Q000378:metabolism*; D007700:Kinetics; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains
D002250:Carbon Radioisotopes; D005561:Formates; C030544:formic acid; D002245:Carbon Dioxide; D005557:Formaldehyde; D003903:Deuterium; D004128:Dimethylnitrosamine