Elimination

The small fraction of unchanged NMP remaining is excreted renally. The metabolites 5-HNMP, MSI and 2-HMSI are readily eliminated via the kidneys (Akesson and Jonsson, 1997; Akesson and Paulsson, 1997).

Unchanged NMP was detected in urine only on day 1 following oral administration of 100 mg NMP (Akesson and Jonsson, 1997). Following inhalation exposure, the mean elimination half-life of NMP in plasma was calculated as 4 hours (range 2.9-5.8 hours) and in urine, 4.5 hours (range 3.5-6.6 hours) (Akesson and Paulsson, 1997). The mean fraction of the orally administered dose of NMP excreted in urine was 0.8% (Akesson and Jonsson, 1997). The 2% fraction of NMP excreted renally following inhalation was possibly overestimated due to concommitant dermal exposure (Akesson and Paulsson, 1997; Akesson and Jonsson, 2000). One third of the ingested NMP was not excreted in the urine and incomplete absorption by the gastrointestinal tract or other, unidentified metabolites may account for the balance (Akesson and Jonsson, 1997).

Following oral administration of 100 mg NMP, 5-HNMP was detected in urine on days 1 and 2 post-exposure. The urinary elimination half-life of 5-HNMP was estimated at 4 hours (Akesson and Jonsson, 1997). The calculated mean 5-HNMP plasma and urine half-lives of 6.3 and 7.3 hours respectively, following inhalation of NMP, may have been influenced by additional NMP absorption across the skin (Akesson and Jonsson, 2000). The mean fraction of the orally administered dose of NMP excreted as 5-HNMP in urine was 44% (Akesson and Jonsson, 1997).

MSI was detected during the first three days post ingestion, with an estimated half-life of eight hours. 2-HMSI was excreted on the first 6 days, with an estimated half-life of 17 hours. Concentrations of NMP and these metabolites were below detection limits on day seven. The mean fractions of the orally administered dose of NMP excreted as MSI and 2-HMSI were 0.4% and 20% respectively (Akesson and Jonsson, 1997).

In rats, the elimination profile from plasma following a single intravenous injection of double-labelled NMP was slow, suggesting slow release into plasma from a deep compartment or storage depot, e.g., fat. There was limited excretion in bile indicating that no enterohepatic circulation occurred. Excretion of radioactivity in urine was found to be the major route of elimination; faeces and carbon dioxide in exhaled air were found to be minor routes of elimination (Wells and Digenis, 1988).

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