Study on in vivo and in vitro metabolism of dimethylformamide in male and female rats.
The study of dimethylformamide (DMF) metabolism by rat tissues in vitro indicates that formaldehyde is not a metabolic product as previously reported [1]. Furthermore, no other monocarbon derivative (CO, CH3OH, HCOOH, CH4) was detected when DMF was incubated with a fortified liver preparation. One metabolic product is methylhydroxymethylformamide (DMF-OH) measured as N-methylformamide (NMF) due to the breakdown of the hydroxymethyl group during gas chromatography. It was usually believed that the main metabolite excreted in urine following administration of DMF to male and female rats was NMF. The results of this study indicate that DMF-OH constitutes the main metabolite in vivo. A quantitatively less important urinary metabolite, hydroxymethylformamide (NMF-OH), is determined as formamide (F) by gas chromatography. In male and female rats, partial hepatectomy reduces markedly the in vivo biotransformation of DMF. Following administration of DMF or NMF, the total amount of metabolites (DMF-OH and/or NMF-OH) excreted in urine is identical in both sexes, but female rats excrete more unchanged parent compound than male rats. The rate of NMF-OH excretion in urine following high doses of DMF supports the hypothesis that DMF may inhibit its own biotransformation.
D000632:Aminopyrine / Q000378:metabolism; D000818:Animals; D001711:Biotransformation; D003035:Cobalt / Q000494:pharmacology; D004126:Dimethylformamide / Q000378:metabolism* / Q000633:toxicity; D004347:Drug Interactions; D005260:Female; D005559:Formamides / Q000652:urine; D007274:Injections, Intraperitoneal; D008099:Liver / Q000378:metabolism*; D008297:Male; D008861:Microsomes / Q000378:metabolism; D010634:Phenobarbital / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D012737:Sex Factors
D005559:Formamides; D000632:Aminopyrine; D003035:Cobalt; D004126:Dimethylformamide; C018021:cobaltous chloride; C002950:methylformamide; D010634:Phenobarbital