Single dose pharmacokinetics of mabuterol in man

The pharmacokinetics of 1-(4-amino-3-chloro-5-trifluoromethyl-phenyl)-2-tert.-butylamino-ethanol hydrochloride (mabuterol), a new bronchodilator in the series of phenyl-ethanolamine derivatives, was investigated in six healthy young male volunteers. Use of tritiated compound allowed characterization of the plasma concentration-time profile of unchanged drug after a single oral dose of 40 micrograms in the form of a drinking solution. Peak concentrations of 96-160 pg/ml were reached between 1.5 and 3.2 h and drug concentrations declined thereafter in a biphasic pattern. Elimination of unchanged drug was slow (t 1/2 beta 20-30 h) due to a low clearance (CL/F 3.0 ml/min/kg) and a large volume of distribution (V beta/F 5.8 l/kg). Absorption of the drug from the gastrointestinal tract was complete and availability of unchanged drug to the systemic circulation could be estimated (F greater than 0.91) using flow model concepts. At peak concentrations mabuterol accounted for only 46% of total radioactivity in plasma but no major conjugated or unconjugated metabolite has been identified. The active tert.-butanol-amino-metabolite was present in negligible amounts (less than 10 pg/ml). The time profile of total radioactivity in plasma closely resembled that reported for structurally related compounds. Excretion of total radioactivity was mainly renal (80% of dose) but the fraction of the dose eliminated unchanged in urine was only 24%. Fecal excretion was low with a cumulative amount recovered over the entire study period of 3%.(ABSTRACT TRUNCATED AT 250 WORDS)