The comparative pharmacokinetics of pentamethylmelamine in man, rat, and mouse
- PMID: 6807560
- DOI: 10.1007/BF00292880
The comparative pharmacokinetics of pentamethylmelamine in man, rat, and mouse
Abstract
The pharmacokinetics of pentamethylmelamine (PMM) have been investigated in mouse (Balb C-, CBA/LAC, nude), rat (Wistar), and man. In all three species, PMM was extensively demethylated to N2,N2,N4,N6-tetramethylmelamine and N2,N4,N6-trimethylmelamine, although marked species differences in the rate of metabolism were observed. PMM metabolism was more rapid in the mouse (plasma t1/2 = less than 15 min) than in the rat (plasma t1/2 = 40 min), and slower in man (plasma t1/2 = 102 min) than in either mouse or rat. Furthermore, the peak plasma concentrations of N-methylolmelamines, intermediates generated during oxidative N-demethylation, were correspondingly higher in the mouse (563-773 microM) than in the rat (211 microM), whilst in man they were undetectable (less than 50 microM). In view of the highly cytotoxic nature of N-methylolmelamines, we conclude that these pharmacokinetic differences may be related to the antitumour effectiveness of PMM in mouse, rat, and man.
Similar articles
-
Preclinical toxicology, pharmacokinetics and formulation of N2,N4,N6-trihydroxymethyl-N2,N4,N6-trimethylmelamine (trimelamol), a water-soluble cytotoxic s-triazine which does not require metabolic activation.Cancer Chemother Pharmacol. 1986;17(3):251-8. doi: 10.1007/BF00256694. Cancer Chemother Pharmacol. 1986. PMID: 3091280
-
Hexamethylmelamine and pentamethylmelamine tissue distribution in M5076/73A ovarian cancer-bearing mice.Cancer Treat Rep. 1982 Jan;66(1):127-33. Cancer Treat Rep. 1982. PMID: 6796267
-
First-pass metabolism of pentamethylmelamine in the rat liver.Cancer Res. 1985 Mar;45(3):983-6. Cancer Res. 1985. PMID: 3918792
-
Pentamethylmelamine: review of an aqueous analog of hexamethylmelamine.Cancer Treat Rep. 1986 Mar;70(3):383-9. Cancer Treat Rep. 1986. PMID: 3082512 Review.
-
N-(Hydroxymethyl) melamines.Gen Pharmacol. 1997 Feb;28(2):177-82. doi: 10.1016/s0306-3623(96)00172-3. Gen Pharmacol. 1997. PMID: 9013191 Review.
Cited by
-
Twenty-sixth annual general meeting of the British Association for Cancer Research (in conjunction with the European Organization for Research and Treatment for Cancer--Pharmacokinetics and Metabolism Group and the Drug Metabolism Group). March 24-27, 1985, Birmingham, U.K.Br J Cancer. 1985 Sep;52(3):409-67. doi: 10.1038/bjc.1985.210. Br J Cancer. 1985. PMID: 4041366 Free PMC article. No abstract available.
-
Pharmacokinetics and metabolism of hexamethylmelamine in mice after IP administration.Cancer Chemother Pharmacol. 1986;18(3):226-30. doi: 10.1007/BF00273391. Cancer Chemother Pharmacol. 1986. PMID: 3100080
-
Phase II trial of trimelamol in refractory ovarian cancer.Br J Cancer. 1991 Feb;63(2):311-3. doi: 10.1038/bjc.1991.72. Br J Cancer. 1991. PMID: 1997112 Free PMC article. Clinical Trial.
-
N-methyl antitumour agents. A distinct class of anticancer drugs?Cancer Chemother Pharmacol. 1987;19(2):91-102. doi: 10.1007/BF00254559. Cancer Chemother Pharmacol. 1987. PMID: 3552281 Review.
-
Whole brain 3D MR fingerprinting in multiple sclerosis: a pilot study.BMC Med Imaging. 2021 May 22;21(1):88. doi: 10.1186/s12880-021-00620-5. BMC Med Imaging. 2021. PMID: 34022832 Free PMC article.