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Clinical Pharmacokinetics of β-Agonists

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Summary

The β-agonists have found wide clinical use as racemic mixtures for 20 years, but information on their pharmacokinetics is not comprehensive. They are well absorbed orally, but have low systemic availability due to extensive first-pass sulphation. When administered by inhalation, very little of the administered dose reaches the lungs, but the small amount that does produces effective bronchodilatation. Plasma protein binding of most β-agonists is negligible, and there is substantial extravascular distribution of the administered dose. Elimination of intravenous drug is predominantly renal, whereas oral doses are mostly eliminated by biotransformation. Renal clearance correlates with creatinine clearance; therefore, dose reduction should be considered if renal function is impaired, such as in the elderly or in cardiac failure. The elimination half-life of most β-agonists is relatively short, and pharmacokinetics are independent of dose and duration of treatment. Differences in the pharmacokinetics of the enantiomers are evident.

There is very large variation in pharmacodynamic response for a given plasma β2-agonist concentration among different subjects, and as treatment proceeds in an individual subject. Therefore, in most cases therapeutic response and side effects are more useful for the monitoring of β2-agonist treatment than measurement of plasma drug concentrations.

The pharmacokinetics of β2-agonists are not greatly altered in pregnancy although these agents cause a marked reduction in maternal renal function. Placental transfer is relatively rapid, and side effects are observed in fetus and neonate. Elimination may be somewhat faster in children (8 to 15 years) than in young adults. Asthma does not appear to influence the pharmacokinetics of β2-agonists; the only recorded drug interaction of clinical significance is an increase in theophylline clearance by intravenous isoprenaline (isoproterenol). Controlled release oral preparations do not reduce side effects, but may improve compliance due to less frequent dosing.

The application of pharmacokinetic principles may improve the clinical usage of β-agonists, at least when they are used in premature labour and in cardiac failure.

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    Denis J. Morgan

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Morgan, D.J. Clinical Pharmacokinetics of β-Agonists. Clin Pharmacokinet 18, 270–294 (1990). https://doi.org/10.2165/00003088-199018040-00002

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