Repeated Administration of d-Amphetamine Results in a Time-dependent and Dose-independent Sustained Increase in Urinary Excretion of p-Hydroxyamphetamine in Mice

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概要

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• The biotransformation of d-amphetamine into p-hydroxyamphetamine (HA) by cytochrome P450 occurs in several species besides humans. The extent of HA excretion varies among species and the oxidative pathway involved in this biotransformation is reported to be implicated in the toxic effects of d-amphetamine. The aim of this study was to evaluate the influence of dose and repeated administration of d-amphetamine on the urinary excretion of d-amphetamine and HA in mice. Charles River Caesarian Derived (CD)-1 mice, kept in metabolic cages, were treated with d-amphetamine (5, 10 and 20mg/kg, i.p., daily, for 14days). Urine was collected at 24hr intervals and analyzed by HPLC for the quantification of d-amphetamine and HA. Urinary excretion of d-amphetamine increased in a dose dependent manner, the urinary levels being fairly constant after the 4th day. On the other hand the urinary excretion of HA increased during the whole time of d-amphetamine dosing and was not dose dependent. Cortical tubule degeneration was observed for the two higher doses, which may explain the HA excretion pattern, although inhibition of cytochrome P450 (CYP) after high d-amphetamine dosing may also be involved.

• 公益社団法人日本薬学会の論文
• 2007-08-01

著者

• Fernandes Eduarda

  REQUIMTE, Departamento de Quimica-Fisica, Faculdade de Farmacia da Universidade do Porto

• Bastos Maria

  REQUIMTE, Departamento de Toxicologia, Faculdade de Farmacia da Universidade do Porto

• Carvalho Felix

  REQUIMTE, Departamento de Toxicologia, Faculdade de Farmacia da Universidade do Porto

• Carvalho Felix

  Requimte Departamento De Toxicologia Faculdade De Farmacia Da Universidade Do Porto

• Fernandes Eduarda

  Requimte Departamento De Quimica-fisica Faculdade De Farmacia Da Universidade Do Porto

• De Lourdes

  Requimte Departamento De Toxicologia

• Bastos Maria

  Requimte Departamento De Toxicologia Faculdade De Farmacia Da Universidade Do Porto

• DUARTE JOSE

  Departamento de Biotecnologia, Azinhaga dos Lameiros a Estrada do Paco do Lumiar

• Carvalho Marcia

  Requimte Toxicology Department Faculty Of Pharmacy University Of Porto

• REMIAO Fernando

  REQUIMTE, Toxicology Department, Faculty of Pharmacy, University of Porto

• PEREIRA Maria

  Departamento de Fisiologia Vegetal, LB. Universidade Estadual de Campinas

• Scares Maria

  REQUIMTE, Department of Toxicology, Faculty of Pharmacy, University of Porto

• Pires-das-Neves Ricardo

  Department of Biology, University of Aveiro, Campus de Santiago

• Duarte Jose

  Department Of Sports Biology Faculty Of Sport Sciences University Of Porto

• Duarte Jose

  Departamento De Biotecnologia Azinhaga Dos Lameiros A Estrada Do Paco Do Lumiar

• Scares Maria

  Requimte Department Of Toxicology Faculty Of Pharmacy University Of Porto

• Pereira Maria

  Department Of Biology University Of Aveiro Campus De Santiago

• Pereira Maria

  Departamento De Fisiologia Vegetal Lb. Universidade Estadual De Campinas

• Remiao Fernando

  Requimte Department Of Toxicology Faculty Of Pharmacy University Of Porto

• Pires-das-neves Ricardo

  Department Of Biology University Of Aveiro Campus De Santiago

• Carvalho Marcia

  Requimte Department Of Toxicology Faculty Of Pharmacy University Of Porto

• Soares Maria

  REQUIMTE, Department of Toxicology, Faculty of Pharmacy, University of Porto

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