Pharmacokinetics and metabolism of hexamethylmelamine in mice after IP administration.
The pharmacokinetics of hexamethylmelamine (HMM) and its first metabolite (hydroxymethylpentamethylmelamine: HMPMM) following IP bolus dose of 200 mg/kg were studied in mice. The drug concentrations were determined by a sensitive reversed-phase HPLC assay. Thus, for the first time, HMM major hydroxylated and demethylated metabolite plasma levels canbedetermined at the same time. Pharmacokinetic data were analyzed by an original method using a nonlinear cost function minimized by a simplex algorithm. An important property of this computer program is that convergence is ensured in contrast to linear or nonlinear least-square regression analysis, which leads to lack of convergence or to false convergence. Both HMM and HMPMM data fit a one-compartment open model. The parameters obtained indicate that the parent drug would probably be rapidly and completely transformed by the human body into HMPMM.
D000465:Algorithms; D006585:Altretamine / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000097:blood / Q000378:metabolism*; D000818:Animals; D055598:Chemical Phenomena; D002621:Chemistry; D006207:Half-Life; D007274:Injections, Intraperitoneal; D007700:Kinetics; D008297:Male; D051379:Mice; D008954:Models, Biological; D014227:Triazines / Q000378:metabolism*
D014227:Triazines; C024065:pentamethylmonomethylolmelamine; D006585:Altretamine; C022048:pentamethylmelamine