Am. J. Respir. Crit. Care Med., Volume 160, Number 4, October 1999, 1136-1141

Preferential Pulmonary Retention of (S)-Albuterol after Inhalation of Racemic Albuterol

RAJIV DHAND, MARK GOODE, RALSTON REID, JAMES B. FINK, PATRICK J. FAHEY, and MARTIN J. TOBIN

Division of Pulmonary and Critical Care Medicine, and Division of Biological Psychiatry, Edward Hines Jr. Veterans Affairs Hospital, and Loyola University of Chicago Stritch School of Medicine, Hines, Illinois

The (R)-enantiomer of racemic albuterol produces bronchodilation, whereas the (S)-enantiomer may increase airway reactivity. After oral or intravenous administration of racemic albuterol, the (R)- enantiomer is metabolized several times faster than the (S)-enantiomer; however, enantiomer disposition after inhaling racemic albuterol with a metered-dose inhaler (MDI) is not known. Accordingly, 10 healthy subjects inhaled racemic albuterol with a MDI alone and with a MDI and holding chamber. We measured plasma levels of unchanged (R)- and (S)-albuterol before and up to 4 h after inhalation of racemic albuterol, and determined the unchanged R/S ratio in urine before and at 0.5, 4, 8, and 24 h later. The disposition of albuterol's enantiomers with a MDI and holding chamber was similar to that with a MDI alone. The area under the curve (AUC) of the plasma levels over time was significantly lower for the (S)- than for the (R)-enantiomer395.5 ± 141.0 (SE) versus 882.7 ± 126.4 ng · ml¹ · min (p < 0.05)indicating preferential retention of (S)-albuterol in the lung. The R/S ratio in urine at 0.5 h after albuterol was > 1, reflecting the higher plasma level of the (R)-enantiomer. In conclusion, preferential retention of the (S)- compared with the (R)-enantiomer in the lung could lead to accumulation of the (S)-enantiomer after long-term use of racemic albuterol.

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