Comparative pharmacokinetics of 1-(2-chloroethyl)-3-(2,6-dioxo-1-piperidyl)-1-nitrosourea in rats and patients and extrapolation to clinical trials.
The plasma pharmacokinetics of 1-(2-chloroethyl)-3-(2,6-dioxo-1-piperidyl)1-nitrosourea (PCNU) were determined in ambulatory rats and in patients receiving PCNU chemotherapy in Phase 1 and II studies. After derivativization to the methyl carbamate, both rat and human PCNU plasma levels were measured by gas chromatography-mass spectrometry. Comparison of the tolerated dose levels and pharmacokinetics of PCNU to the values determined for 1,3-bis(2-chloroethyl)-1-nitrosourea in humans indicated that PCNU has a lower plasma drug area under the curve at equitoxic doses. We conclude that PCNU may show less clinical efficacy than 1,3-bis(2-chloroethyl)-1-nitrosourea in the treatment of solid tumors.
D000818:Animals; D002330:Carmustine / Q000097:blood / Q000627:therapeutic use; D002986:Clinical Trials as Topic; D004341:Drug Evaluation; D008401:Gas Chromatography-Mass Spectrometry; D006801:Humans; D007700:Kinetics; D009150:Mustard Compounds / Q000097:blood / Q000627:therapeutic use / Q000633:toxicity; D009369:Neoplasms / Q000188:drug therapy; D009607:Nitrosourea Compounds / Q000097:blood* / Q000627:therapeutic use / Q000633:toxicity; D051381:Rats
D009150:Mustard Compounds; D009607:Nitrosourea Compounds; C018627:1-(2-chloroethyl)-3-(2,6-dioxo-3-piperidinyl)-1-nitrosourea; D002330:Carmustine