Bioavailability of (+)-methamphetamine in the pigeon following an intramuscular dose

Abstract

Pigeons are used frequently as subjects in behavioral pharmacology research. An advantage of the pigeon is an exceedingly vascular breast muscle, which is easily accessible for injections. The purpose of these studies was to provide a profile of the pharmacokinetics of (+)-methamphetamine (METH) and (+)-amphetamine (AMP), a pharmacologically active metabolite, in pigeons (n=6) after intramuscular (i.m.) and intravenous (i.v.) dosing (0.8 mg/kg). LC-MS/MS analysis was used to determine serum concentrations of METH and AMP. A modified crossover design was used to determine the bioavailability, time to maximum concentration, total clearance, the volume of distribution, the maximal concentration, the area under the concentration-time curve (AUC), and terminal elimination half-life for METH. The route of administration did not significantly affect these pharmacokinetic parameters. The time to maximum concentration for METH and AMP following i.m. administration was 0.3 h. Maximum AMP serum concentrations were achieved in 2 h, irrespective of the route of administration, and these concentrations remained essentially constant for an additional 6 h. The metabolism of METH to AMP was not affected by the route of administration, and the molar ratio AMP to METH AUC values were the same (i.v.=0.57; i.m.=0.41). These results show that METH pharmacokinetics after i.m. administration in the pigeon are similar to i.v. administration. Thus i.m. is a reasonable route of administration for METH behavioral assays in the pigeon if sufficient time for absorption is given following the dose, and the behavioral endpoint is not dependent on the rapid input of METH following an i.v. dose.

Figure 1

Serum concentration-time profiles for (+)-methamphetamine (METH) and (+)-amphetamine (AMP) following either intravenous (▽, AMP and □, METH) or intramuscular (△, AMP and ○, METH) administration of 0.8 mg/kg METH to pigeons.