Following administration of 3 ascending dose inhalations, a fourth session was conducted to contrast the effects of a prototypic alpha agonist phenylephrine, (Gensia Sicor Pharmaceuticals, Irvine, CA) with those produced by inhaled methamphetamine and to administer a parenteral dose of l-methamphetamine that would allow determination of absolute bioavailability. A similar phenylephrine challenge procedure has been safely used to measure hemodynamic response in hypertensive patients maintained off all antihypertensive medication for 2 weeks [8]. The phenylephrine response test was performed by giving an intravenous phenylephrine bolus dose of 100 Îg. If the initial dose did not produce a 15 mm rise in systolic blood pressure within 15 minutes, a second 200 Îg dose was given at 30 minutes. Two hours after the last phenylephrine dose, a slow (over 15 minutes) intravenous infusion of 5 mg of l-methamphetamine was administered to establish absolute bioavailability. The l-methamphetamine was prepared from the free base obtained from Sigma (St. Louis, MO) under FDA IND 58,189. We had planned to quantify relative bioavailability by extracting and quantifying the residual l-methamphetamine content from the inhalers. However, the amount of l-methamphetamine in new inhalers was highly variable (between 50 and 75 mg) and, given the small delivered doses, we were not able to obtain sufficiently accurate inhaler weights before and after dosing to allow estimation of delivered doses.




Vicks Inhaler Meth Recipe