ISSN:
1432-0843
Source:
Springer Online Journal Archives 1860-2000
Topics:
Medicine
Notes:
Summary 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 =〈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 μM) than in the rat (211 μM), whilst in man they were undetectable (〈50 μM). 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.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1007/BF00292880
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