The correlation of urinary levels of albuterol and its metabolites isomers following inhalation from a dry powder inhaler and in vitro particle size characterisation

This study was designed to analyse the two enantiomers of abuterol in urine after the inhalation of a single dose of racemic albuterol from three dry powder inhalers by human volunteers. Urine samples were collected over 24 h and analysed by HPLC-with fluorescence detection. Albuterol and its metabolites in urine could only have resulted from pulmonary absorption because gastrointestinal absorption was prevented. Unchanged albuterol and its conjugated metabolites were detected in the urine of healthy volunteers at much higher levels than in the urine of the asthmatics. Also, the amount of S-(+)-isomer excreted in urine was higher than that of the R-(−)-isomer. These differences did not arise as a consequence of either the formulation or the inter-conversion of two isomers in the urine. There is a relationship between the improvement of mid-expiratory flow (FEF25–75) and the amount of R-(−)-albuterol remaining to be excreted. The elimination rate constants of the parent drug in healthy volunteers of both R-(−)- and S-(+)-isomers were higher than those of the respective conjugated metabolites. The mean S/R ratio of the parent drug was about unity initially and increased to about 1.5 in the urine collected between 12 and 24 h. The values of S/R ratio of the conjugated metabolites in the healthy volunteers were in the range 1.2–2.4, with the value increasing over the time of collection before reaching a plateau. This also occurred with the asthmatics, but the ratios were higher, in the range of 2.0–4.5. In summary, the urinary level of albuterol following in vivo inhalation was found to correlate with in vitro deposition data from the dry powder inhaler.