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 (IM) and intravenous (IV) 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 IM 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 (IV=0.57; IM=0.41). These results show that METH pharmacokinetics after IM administration in the pigeon are similar to IV administration. Thus IM 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 IV dose.

Cytochrome P450-2D6 extensive metabolizers are more vulnerable to methamphetamine-associated neurocognitive impairment: Preliminary findings

“…Although no study to our knowledge has examined the effect that different routes of administration may have on meth metabolism, recent work (Hendrickson et al, 2008) with pigeons suggests that administration of meth either intramuscularly or intravenously does not affect metabolism. Nevertheless, route of administration should be examined in future investigations, given that it results in differences in bioavailability.…”

Sex differences in methamphetamine use disorder perused from pre-clinical and clinical studies: Potential therapeutic impacts

“…METH pharmacokinetics have been studied under various conditions by several groups of investigators ( Berquist et al, 2020 ; Hendrickson et al, 2008 ; Milesi-Halle et al, 2015 ; Rambousek et al, 2014 ). Milesi-Halle et al (2005) reported on sex- and dose-differences in the pharmacokinetics of METH and amphetamine (AMPH) in male and female Sprague-Dawley rats after administering 1.0 and 3.0 mg/kg METH doses.…”

Impact of methamphetamine on infection and immunity

“…absorption was three times higher than i.m. In this regard, some studies support that injection of METH in ranges of 3.6–10 mg/Kg are considered lethal in animals (Hendrickson et al, 2008 ). Similarly, a recent study showed an 8-fold higher catalytic activity of METH in rhesus macaques compared to humans due to enzymatic differences (Earla et al, 2014 ).…”