The relative bioavailability of metaproterenol (3,5-dihydroxy-a-[(isopropylamino)methyl]benzyl alcohol) following a single dose (10-mg metaproterenol sulfate tablet) was studied in six normal male volunteers using coadministration of a solution of a deuterated analogue (metaproterenol-d, sulfate). The bioavailability of the tablet formulation relative to that of the oral solution was 92 2 9%, with excellent power at the 5% significance level. Comparison of the coadministration of the labeled and unlabeled metaproterenol sulfate solutions in two subjects after a one-week washout demonstrated the absence of an isotope effect on either absorption or elimination. A GC-MS assay for metaproterenol was developed to measure plasma concentrations resulting from oral administration. The assay was linear over the range of 0.5-8 ng/ mL, corresponding to typical plasma metaproterenol concentrations obtained after a single 10-mg oral dose. Accuracy and precision data were obtained at metaproterenol concentrations of 1 .O and 2.0 ng/mL plasma to demonstrate the applicability of the assay for bioavailability studies. Following oral administration, rnetaproterenol showed peak plasma concentrations of 2.2 to 13 ng/mL at 0.75 to 3.0 h, with a terminal harmonic mean half-life of 2.1 h over the plasma concentration range studied. The renal clearance of 133-158 mUmin for metaproterenol slightly exceeds the glomerular filtration rate in humans. Metaproterenol (3,5-dihydroxy-a-[(isopropylamino)methyllbenzyl alcohol, 1) is a potent P-adrenoceptor agonist with a rapid onset of action when given by inhalation therapy. For the management of pulmonary function between inhalations in patients with asthma, bronchitis, and emphysema, 10-20mg tablets of the sulfate form of the drug, taken orally three to four times daily, are often recommended.' Human studies have shown that metaproterenol is a more specific pz sympathomimetic than isoproterenol in that it causes less tachycardia and hypotension at doses that are equipotent for bronchodilation.2 Following a n oral dose, metaproterenol is extensively metabolized in the gastrointestinal tract3 to the 3-0-sulfate conjugate of metaproterenoL4.6 This is consistent with the fate of other oral bronchodilators of the hydroxyphenethylamine class which undergo extensive first-pass intestinal degradation.6 Urine excretion of free metaproterenol following oral dosing and intravenous infusion demonstrated that < 15% of the drug is absorbed intact.3~~ Because