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Population pharmacokinetics of (R)-albuterol and (S)-albuterol in pediatric patients aged 4-11 years with asthma.

Author(s): Maier G, Rubino C, Hsu R, Grasela T, Baumgartner RA

Affiliation(s): Clinical Pharmacology, Sepracor Inc., 85 Waterford Drive, Marlborough, MA 01752-7010, USA. gmaier@sepracor.com

Publication date & source: 2007, Pulm Pharmacol Ther., 20(5):534-42. Epub 2006 May 27.

Publication type: Comparative Study; Randomized Controlled Trial; Research Support, Non-U.S. Gov't

OBJECTIVE: To characterize the population pharmacokinetics (PK) of (R)- and (S)-albuterol in pediatric asthmatics using a model that supports a sparse blood sampling strategy. METHODS: The data for this analysis were collected from patients enrolled in a randomized, double-blind, multicenter, placebo- and active-controlled study evaluating the safety and efficacy of levalbuterol in asthmatic children aged 4-11 years. Patients received either levalbuterol 0.31 mg, levalbuterol 0.63 mg, racemic albuterol 1.25 mg, or racemic albuterol 2.5 mg via nebulizer. Separate population pharmacokinetic models were developed for (R)- and (S)-albuterol using the NOMNEM((R)) computer program. Covariate models were developed to identify significant predictors of inter-patient variability. RESULTS: A total of 995 samples and 262 patients were used for the (R)-albuterol population PK model while a total of 496 samples and 128 patients were used for the (S)-albuterol population PK model. The apparent clearance of (R)-albuterol was much more rapid than that of (S)-albuterol (approximately four-fold higher), and the apparent volume of distribution was much larger for (R)-albuterol (in part due to pre-systemic metabolism) than for (S)-albuterol (approximately four-fold higher). CONCLUSIONS: In this study of pediatric patients, the models were able to demonstrate using two to four samples per patient that the apparent clearance and volume of distribution of (R)-albuterol were several fold higher than that of (S)-albuterol. The pharmacokinetics of (R)-albuterol were similar after administration of levalbuterol or racemic albuterol and were linear over the examined dose range (0.31-0.63 mg nebulized dose). The presence of (S)-albuterol did not significantly alter the pharmacokinetics of (R)-albuterol, suggesting that effects of (S)-albuterol may be due to the intrinsic pharmacology of this isomer.

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