Pentamethylmelamine (PMM): Phase I clinical and pharmacokinetic studies.
PMM is a water-soluble alternative to HMM. PMM has been administered as an intravenous infusion to 17 patients in a Phase I clinical trial. The dose-limiting toxicities were nausea and vomiting which were observed in all patients at 500 mg m-2 and above. The dose was not escalated above 1300 mg m-2 where nausea and vomiting were severe, prolonged (greater than 24 h) and poorly controlled by anti-emetics. Haematological, hepatic and renal toxicities were not observed. Neurological toxicity was not observed at low doses (less than 500 mg/m2) but could not be determined at higher doses due to intensive anti-emetic therapy. Pharmacokinetic studies (100-500 mg m-2) indicated that PMM plasma levels are dose-dependent and that the PMM disposition-phase half-life is prolonged in patients with abnormal liver function. It is concluded that the severe toxicity of PMM will limit the clinical utility of this compound and hence Phase II trials are not recommended.
D000328:Adult; D000368:Aged; D006585:Altretamine / Q000009:adverse effects / Q000031:analogs & derivatives / Q000097:blood / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D005260:Female; D006801:Humans; D007700:Kinetics; D008099:Liver / Q000503:physiopathology; D008113:Liver Neoplasms / Q000556:secondary; D008297:Male; D008875:Middle Aged; D009325:Nausea / Q000139:chemically induced; D009369:Neoplasms / Q000188:drug therapy*; D009422:Nervous System Diseases / Q000139:chemically induced; D014227:Triazines / Q000627:therapeutic use*; D014839:Vomiting / Q000139:chemically induced
D000970:Antineoplastic Agents; D014227:Triazines; D006585:Altretamine; C022048:pentamethylmelamine