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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

Pharmacological disposition of 1-(2-chloroethyl)-3-(2,6-dioxo-3-piperidyl)-1-nitrosourea in mice.

1-(2-Chloroethyl)-3-(2,6-dioxo-3-piperidyl)-1-nitrosourea (PCNU; NSC 95466) is a lipid-soluble nitrosourea that is presently in clinical trial. We have studied the pharmacological disposition of [ethyl-14C]PCNU in mice using an i.v. drug dose of 20 mg/kg/animal. Disappearance of total radioactivity from plasma was biphasic with mean half-lives of the two exponential phases of 21.7 min and 27.4 hr, respectively. The plasma half-life of intact drug was 29 min, and levels of intact drug, as measured by thin-layer chromatography, fell below detectable levels by 4 hr. The area under the plasma concentration-time curve for intact drug was 32.72 nmol X hr/ml. Computer analysis of the data for total radioactivity (PCNU equivalents), based upon an open two-compartment model, yielded values of the pharmacokinetic parameters K12, K21, and K10 of 1.49 hr-1, 0.25 hr-1, and 0.19 hr-1, respectively. The highest peak organ level of drug was 168.9 nmol of PCNU equivalents per g tissue in the liver 1 hr after drug administration. Maximum levels in kidney, lungs, heart, and spleen were observed at 5 min, with values of 119.5, 115.4, 80.3, and 66.7 nmol of PCNU equivalents per g of tissue, respectively. A high peak drug level in brain (50.6 nmol/g) agreed with the prediction that PCNU can cross the blood-brain barrier. The levels of intact drug relative to total radioactivity at 30 min were 60% in brain, 55% in heart, and 48% in spleen. The concurrent value in liver was 7% of the total radioactivity, suggesting that metabolism or decomposition of PCNU occurs in this organ. The principal excretory route of [ethyl-14C]PCNU was urinary, with a cumulative excretion of 62% in the first 24 hr.[1]


  1. Pharmacological disposition of 1-(2-chloroethyl)-3-(2,6-dioxo-3-piperidyl)-1-nitrosourea in mice. Rahman, A., Luc, P.V., Schein, P.S., Woolley, P.V. Cancer Res. (1984) [Pubmed]
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