title: Pharmacokinetics of hexamethylmelamine administered via the Ip route in an oil emulsion vehicle.
abstract: 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.
mesh_terms: 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*
chemical_list: D005217:Fat Emulsions, Intravenous; D014227:Triazines; D012965:Sodium Chloride; D006585:Altretamine