Pharmacokinetics of hexamethylmelamine administered via the Ip route in an oil emulsion vehicle.
Saline and Intralipid were compared as vehicles for the ip administration of hexamethylmelamine (HMM) in mice. The drug proved stable over at least 7 weeks in solution and 2 years in crystal form. Fiftyfold higher concentrations of HMM could be achieved in Intralipid than in saline. The peritoneal pharmacokinetics were first-order and linear over the concentration range of HMM in Intralipid from 50 to 2000 micrograms/ml. The mean peritoneal half-life of HMM in Intralipid was 12.5-fold greater than the mean half-life of HMM in saline at the same concentration. Peritoneal concentration X time drug exposure, as measured by the area under the curve in single-dose elimination experiments, was 1200-fold greater for HMM at 2000 micrograms/ml in Intralipid than at 50 micrograms/ml, near saturation, in saline. The steady-state peritoneal to plasma concentration ratios were 96-104 for HMM in Intralipid at concentrations of 300-2000 micrograms/ml, and the peritoneal concentration that could be maintained by the constant ip infusion of HMM at 2000 micrograms/ml in Intralipid was at least 1600-fold greater than that maintainable with HMM in saline. The mean peritoneal clearance calculated by two independent methods and at three different concentrations of HMM in Intralipid was 0.112 +/- 0.016 ml/minute. HMM in Intralipid is a stable formulation that can be used to increase peritoneal exposure to HMM and may potentially be used iv as well.
D006585:Altretamine / Q000008:administration & dosage* / Q000378:metabolism; D000818:Animals; D005217:Fat Emulsions, Intravenous; D006207:Half-Life; D007274:Injections, Intraperitoneal; D051379:Mice; D010529:Peritoneal Cavity / Q000378:metabolism; D012965:Sodium Chloride; D014227:Triazines / Q000008:administration & dosage*
D005217:Fat Emulsions, Intravenous; D014227:Triazines; D012965:Sodium Chloride; D006585:Altretamine