Metabolism

NMP is readily converted to three polar metabolites, 5-hydroxy-N-methylpyrrolidone (5-HNMP), N-methyl succinimide (MSI) and 2-hydroxy-N-methylsuccinimide (2-HMSI). These compounds are not detected in unexposed subjects (Akesson and Jonsson, 1997).

In rats, the liver is thought to be the main site of NMP metabolism. Minor routes of metabolism with differing rates are thought to account for the remainder. Three metabolites were detected (Wells and Digenis, 1988), and one was identified as 5-HNMP (Wells et al., 1992).

In humans, 5-HNMP is the major metabolite identified (Akesson and Jonsson, 1997). A close correlation was observed between plasma and urine 5-HNMP concentrations and air NMP concentrations (Akesson and Jonsson, 2000). It is postulated that NMP is primarily hydroxylated to 5-HNMP, which is then oxidised to MSI, and this in turn is further hydroxylated to 2-HMSI. However, another as yet unidentified metabolite was eluted before 5-HNMP (Akesson and Jonsson, 1997).

Neither 5-HNMP nor 2-HMSI undergo conjugation with glucuronic acid or sulphate (Akesson and Jonsson, 1997). Conjugates of the major metabolite resulting after acid hydrolysis (not identified but proposed to be 4-(methylamino)butanoic acid) were not detected in rat urine after a single intravenous injection of doublelabelled NMP (Wells and Digenis, 1988). One glucuronide was detected in the urine of a one day old neonate following chronic exposure to ethosuximide, a succinimide thought to undergo metabolism similar to NMP (Horning et al., 1973; Akesson and Jonsson, 1997).

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