PHARMACOKINETICS OF (R,S)-ALBUTEROL AFTER AEROSOL INHALATION IN HEALTHY ADULT VOLUNTEERS

The pharmacokinetics of inhaled (R,S)-albuterol following pulmonary ab sorption were studied in healthy human subjects. Ten subjects (5 femal es and 5 males) inhaled two puffs (180 mu g) of albuterol via a metere d-dose inhaler and spacer device. All subjects were nonsmoking and had normal pulmonary function. Charcoal slurries were ingested to block g astrointestinal absorption of drug. Venous samples were obtained from each subject at thirteen time points from 0 through 12 h post dose. (R ,S)-Albuterol concentration in plasma was measured using a gas chromat ography-mass spectrometry (GC-MS) assay. The plasma concentration-time profiles conformed to a two-compartment extravascular model with firs t-order absorption kinetics. The drug levels reached maximum in 12.6 /- 2.2 (SD) minutes, which is in contrast with previous reports that m aximum plasma concentrations occur within 2 to 4 h. The mean peak plas ma level was 1469 +/- 410 pg/mL. The mean half-life of distribution wa s 17.9 +/- 8.2 min. The mean half-life of elimination was 4.4 +/- 1.5 h. Female subjects achieved peak concentration more rapidly than male subjects (10.4 vs 14.8 min, p = 0.01) and had a higher mean peak conce ntration (1778 vs 1159 pg/mL, p = 0.04).