title: Spontaneous locomotor activity and pharmacokinetics of intravenous methamphetamine and its metabolite amphetamine in the rat.
abstract: The purpose of these studies was to better understand the behavioral effects and pharmacokinetics of an i.v. bolus dose of (+)-methamphetamine [(+)-METH] in a rat model of (+)-METH abuse. We characterized the behavioral effects after increasing (+)-METH doses (0.1, 0.3, and 1.0 mg/kg) and the pharmacokinetics of (+)-METH (and its metabolite (+)-amphetamine [(+)-AMP)]) at the lowest and highest of these doses in adult male Sprague-Dawley rats. The doses and route of administration were selected to mimic aspects of human use on a dose/body weight basis. Although the 0.1 mg/kg dose did not cause statistically significant increases in locomotor activity compared with saline controls, the higher doses (0.3 and 1.0 mg/kg) caused statistically significant increases in locomotor activity (p <.05), which lasted for up to 3 h at the highest dose. After the 1.0 mg/kg dose, the volume of distribution at steady state was 9.0 liters/kg, the total clearance was 126 ml/min/kg, and the average distribution and elimination half-lives were 9.2 and 63.0 min, respectively. Because the pharmacokinetic values after the 0.1 mg/kg dose were not different from those after the 1.0 mg/kg dose, the pharmacokinetics of (+)-METH were considered to be independent of the dose over this 10-fold range. (+)-AMP serum concentrations after the 1.0 mg/kg dose peaked from 10 to 30 min, and exhibited a T(1/2lambdaz) of 98.5 min. The statistically longer T(1/2lambdaz) of (+)-AMP (p <.05) suggested that the (+)-AMP terminal elimination rate and not the (+)-AMP metabolic formation rate is the rate-limiting step in (+)-AMP elimination following i.v. (+)-METH dosing.
authors.affiliation: Department of Pharmacology and Toxicology, College of Medicine, University of Arkansas for Medical Sciences, Little Rock, Arkansas 72205, USA.
authors.forename: G J
authors.initials: GJ
authors.lastname: Rivière
authors.forename: K A
authors.initials: KA
authors.lastname: Byrnes
authors.forename: W B
authors.initials: WB
authors.lastname: Gentry
authors.forename: S M
authors.initials: SM
authors.lastname: Owens
mesh_terms: D000661:Amphetamine / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology*; D000818:Animals; D019540:Area Under Curve; D000697:Central Nervous System Stimulants / Q000008:administration & dosage / Q000494:pharmacology*; D007275:Injections, Intravenous; D008297:Male; D008694:Methamphetamine / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology*; D009043:Motor Activity / Q000187:drug effects*; D011485:Protein Binding; D051381:Rats; D017207:Rats, Sprague-Dawley; D013268:Stimulation, Chemical
chemical_list: D000697:Central Nervous System Stimulants; D008694:Methamphetamine; D000661:Amphetamine