Influence of ethanol on metabolism of methamphetamine in rats including hair analysis.
To investigate possible influences of ethanol (EtOH) on metabolism of methamphetamine (MA), dark agouti (DA) rats were assigned to 3 groups including EtOH mono-dosing group, MA mono-dosing group and combined dosing group of EtOH and MA. Following successive administration of respective drugs, time-course changes of plasma and urine levels of EtOH and its metabolites, as well as alterations of plasma, urine, hair levels of the MA and its metabolites, were monitored. Preliminary hydrolysis of the glucuronate conjugates was required because parahydroxymethamphetamine (p-OHMA) and parahydroxyamphetamine (p-OHAP) were promptly conjugated with glucuronic acid in the body. When compared with EtOH group, the maximum plasma concentration of EtOH occurred with some delay in EtOH + MA group, suggesting possibility of some delay of its metabolism. MA concentrations in EtOH + MA group were slightly higher until 6 hours after administration when EtOH was detectable in the blood whereas concentrations of amphetamine (AP) in EtOH + MA group were less, on the contrary. Concentrations of p-OHMA and p-OHAP were obviously less in EtOH + MA group. These findings indicate that N-demethylation and parahydroxylation of aromatic ring of MA would be inhibited in the presence of EtOH. Concentrations of MA and AP in hair were higher in EtOH + MA group. Not only difference in AUC but also possible increase in uptake of the drugs into hair could likely account for this phenomenon.
Yamada
T
T
Department of Legal Medicine, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-ku, 113-8602 Tokyo, Japan.
Hayashida
M
M
Nihira
M
M
D000661:Amphetamine / Q000378:metabolism; D000818:Animals; D004347:Drug Interactions; D000431:Ethanol / Q000378:metabolism / Q000494:pharmacology*; D006197:Hair / Q000378:metabolism*; D008297:Male; D008694:Methamphetamine / Q000378:metabolism*; D051381:Rats
D000431:Ethanol; D008694:Methamphetamine; D000661:Amphetamine