[The effect of ethanol on the metabolism of methamphetamine]

In order to clarify the effects of ethanol (EtOH) on metabolism of methamphetamine hydrochloride (MA-HCl), the plasma and urine samples were taken from three groups of three male crab-eating monkeys (Macaca fascicularis). MA-HCl was given to the first group, both MA-HCl and EtOH were given once to the second group, the after consecutive administration of EtOH for four weeks, both MA-HCl and EtOH were given to the third group. Comparisons were made of the sequential change in the concentration of unchanged methamphetamine (MA) and its supposed metabolites, amphetamine (AP), p-hydroxymethamphetamine (p-HOMA), and p-hydroxyamphetamine (p-HOAP). Additional hematological and plasma-biochemical tests were performed to monitor the influences under the administration of MA-HCl and EtOH on the animals. For the extraction of MA and its metabolites from blood and urine, a solid phase extraction was carried out with which an excellent recovery was achieved. Gas chromatography mass spectrometry (GC-MS) was used to measure the metabolites after changing them to the form of TFA derivative, producing good results. EtOH concentration in the blood was measured by GC using a head-space method. The biological half-life (t1/2) of MA tended to be shortened slightly in the plasma when EtOH was given consecutively. The maximum concentration of AP obtained by administration of EtOH was half that obtained by single administration of MA-HCl and the detectable time was shortened. A high concentration of p-hydroxy metabolites that the been almost undetectable when both MA-HCl and EtOH were administered once, was detected when EtOH was administered consecutively, compared with that when only MA-HCl was administered. Particularly, considerable amounts of p-HOAP was detected even after 72 hours. The trends seen in the excretion of MA and its metabolites into the urine were the same as seen in their plasma concentrations, although there was a difference in the detectable time. The urine collected in a metabolic cage for the monkey was contaminated with drinking water, so that the total amounts of metabolites, rather than sequential change as in the case of plasma, were considered to be of greater significance. When EtOH was administered consecutively, the excreted amounts of p-HOAP in the urine increased saliently and characteristically.(ABSTRACT TRUNCATED AT 400 WORDS)