The Study of In Vitro-In Vivo Correlation: Pharmacokinetics and Pharmacodynamics of Albuterol Dry Powder Inhalers

The pharmacokinetics and pharmacodynamics of albuterol were studied following inhalation of three different in‐house dry powder formulations in healthy volunteers and in asthmatics. Albuterol in plasma was measured using liquid chromatography‐mass spectrometry (LC‐MS). The plasma concentration time profiles were fitted to a two‐compartment model with first‐order kinetics. Oral absorption of swallowed albuterol was eliminated by oral dosing of 560 mg activated charcoal 1 h prior to albuterol aerosol administration. The peak concentration was reached within 15-20 min. Mean peak concentrations in healthy volunteers (six males and six females) were 1.74 ± 0.34, 2.01 ± 0.35, and 2.59 ± 0.27 ng/mL following inhalation of formulations with fine particle doses (FPDs) of 100, 120, and 160 μg of albuterol, respectively. The corresponding peak plasma concentrations of 1.23 ± 0.29, 1.37 ± 0.13, and 1.53 ± 0.11 ng/mL were obtained when asthmatics (six males and six females) were dosed with the same three formulations. The FPD of each formulation correlated well with the area under the curve of plasma concentration-time (AUC0-8) profile. Plasma potassium did not show any significant change over a period of 8 h. The forced vital capacity (FVC), the force expiratory volume in 1 s (FEV1), and mid expiratory flow (FEF25-75) did not correlate with FPD for the three different formulations.