No abstract

Albuterol, a beta-adrenergic agonist bronchodilator, was studied in 12 healthy male volunteers to evaluate the steady-state pharmacokinetics following oral administration of 4-mg tablets, given every six hours for five days. The kinetics of albuterol were best described by a two-compartment open model with first-order absorption kinetics. Steady-state plasma levels were predictable from the kinetic data and were reached by the third day of dosing (ninth and tenth dose). Small accumulation ratios of approximately two were seen based on area under the plasma concentration-time curve and maximal and minimal concentration data. The elimination phase half-life was determined to be 6.5 hours, which is similar to the values reported following single-dose administration.

A highly sensitive and specific quantitative assay for the determination of albuterol in human plasma, based on selected ion monitoring gas chromatography chemical ionization mass spectrometry, has been developed. The [MH]+ ions from the tri-TMS derivatives of albuterol (m/z 456) and the internal standard (2H3)albuterol (m/z 459), were assayed simultaneously by selected ion monitoring. The lower limit of quantitation is 0.25 ng ml-1 and the average assay precision (CV) for albuterol concentrations ranging from 0.25 ng ml-1 to 25 ng ml-1 is approximately 4%. This method is currently being employed for the routine quantitation of albuterol in plasma following the administration of doses therapeutically effective to man.

A new controlled-release (CR) dosage formulation of albuterol has been developed which is suitable for twice-a-day dosing. The present study was conducted in twelve healthy adult male volunteers to compare the steady state plasma levels obtained following repeated administration of a 4 mg CR tablet (q12h) compared to a 2 mg conventional table (q6h) for 5 consecutive days. The mean steady state plasma level-time curves for both the CR and conventional tablet treatments were comparable over time and reproducible. There were no significant differences in the AUC or Cmax values between the two treatments. The mean 48-h AUC values were 240.7 and 231.3 h X ng ml-1 for the conventional and CR tablets, respectively, while the corresponding Cmax values ranged from 5.3 to 6.8 ng ml-1 and 5.4 to 6.5 ng ml-1. There were no significant differences in Cmin values except for one 12-h (day 4) value. Cmin values ranged from 3.8 to 4.3 ng ml-1 and 3.0 to 4.8 ng ml-1 for the conventional and CR tablets, respectively. The data show that the 4 mg albuterol CR tablet (q12h) is bioequivalent to a 2 mg conventional albuterol tablet (q6h). The CR tablet formulation will offer the advantage of increased patient compliance; additionally, the CR formulation may prove to be especially beneficial in the treatment of nocturnal asthma.