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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abstract

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 24 hr intervals and analyzed by HPLC for the quantification of d-amphetamine and HA. Urinary excretion of damphetamine 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.

keywords

ACUTE-RENAL-FAILURE; ISOLATED RAT HEPATOCYTES; ECSTASY MDMA; IN-VITRO; METHAMPHETAMINE; HYPERTHERMIA; INVOLVEMENT

subject category

Toxicology

authors

Carvalho, F; Soares, ME; Fernandes, E; Remiao, F; Carvalho, M; Duarte, JA; Pires-das-Neves, R; Pereira, MD; Bastos, MD

our authors

foto Maria de Lourdes Gomes Pereira

Maria de Lourdes Gomes Pereira

Associate Professor with Aggregation

Groups

G5 - Biomimetic, Biological and Living Materials

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Publication Details

type
Journal Article
year
2007
journal
JOURNAL OF HEALTH SCIENCE
volume
53
publisher
PHARMACEUTICAL SOC JAPAN
issn
1344-9702
issue
4
digital object identifier
10.1248/jhs.53.371
web of science article identifier
WOS:000249350800004

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