The pharmacokinetic parameters of (R)-and (S)-albuterol in children with asthma were obtained using population pharmacokinetic analysis. These data arepresented in Table 2. For comparison, adult data obtained by conventional pharmacokinetic analysis from a different study also are presented in Table 2. In children, AUC and Cmax of (R)-albuterol following administration of 0.63 mg Xopenex Inhalation Solution were comparable to those following admin-istration of 1.25 mg racemic albuterol sulfate inhalation solution.

When the same dose of 0.63 mg of Xopenex was given to children and adults, the predicted Cmax of (R)-albuterol in children was similar to that in adults(0.52 vs. 0.56 ng/mL), while predicted AUC in children (2.55 ng•hr/mL) was about 1.5-fold higher than that in adults (1.65 ng•hr/mL). These data sup-port lower doses for children 6-11 years old compared with the adult doses (see DOSAGE AND ADMINISTRATION).

Table 2: (R)-Albuterol Exposure in Adults and Pediatric Subjects (6-11 years)

Metabolism and Elimination

Information available in the published literature suggests that the primary enzyme responsible for the metabolism of albuterol enantiomers in humans isSULT1A3 (sulfotransferase). When racemic albuterol was administered either intravenously or via inhalation after oral charcoal administration, there wasa 3- to 4-fold difference in the area under the concentration-time curves between the (R)- and (S)-albuterol enantiomers, with (S)-albuterol concentrations being consistently higher. However, without charcoal pretreatment, after either oral or inhalation administration the differences were 8- to 24-fold,suggesting that (R)-albuterol is preferentially metabolized in the gastrointestinal tract, presumably by SULT1A3.

The primary route of elimination of albuterol enantiomers is through renal excretion (80% to 100%) of either the parent compound or the primarymetabolite. Less than 20% of the drug is detected in the feces. Following intravenous administration of racemic albuterol, between 25% and 46% ofthe (R)-albuterol fraction of the dose was excreted as unchanged (R)-albuterol in the urine.

Special Populations

Hepatic Impairment: The effect of hepatic impairment on the pharmacokinetics of Xopenex Inhalation Solution has not been evaluated.

Renal Impairment: The effect of renal impairment on the pharmacokinetics of racemic albuterol was evaluated in 5 subjects with creatinine clearanceof 7 to 53 mL/min, and the results were compared with those from healthy volunteers. Renal disease had no effect on the half-life, but there was a 67%decline in racemic albuterol clearance. Caution should be used when administering high doses of Xopenex Inhalation Solution to patients with renalimpairment.

Pharmacodynamics (Adults and Adolescents ≥ 12 years old)

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