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Pharmacokinetic Optimisation of Asthma Treatment

  • Review Article
  • Pharmacokinetics-Therapeutics
  • Published:
Clinical Pharmacokinetics Aims and scope Submit manuscript

An Erratum to this article was published on 01 August 1994

Summary

Asthma is generally managed with bronchodilator therapy and/or anti-inflammatory drugs. Guidelines now advocate selection of drugs and pharmaceutical formulations (long-acting vs short-acting, inhaled vs systemic) on the basis of disease severity.

Theophylline has a narrow therapeutic margin. Clearance is highly variable and plasma concentrations should be monitored to avoid the occurrence of plasma concentration-related adverse effects. The rate of absorption of theophylline differs depending on the sustained release formulation administered. Some products do not provide sufficient plasma drug concentrations for therapeutic efficacy over a 12-hour period, particularly in patients with high clearance rates (e.g. children and patients who smoke).

Administration of drugs via inhalation offers several advantages over systemic routes of administration (e.g. adverse effects are decreased). Inhalation is now advocated as first-line therapy. Aerosol medications available for the treatment of asthma are β2-agonists (including the newer long-acting agents such as salmeterol), corticosteroids, anticholinergic drugs, sodium cromoglycate (cromolyn sodium) and nedocromil. To reach the airways, aerosolised particles should be 1 to 5µm in diameter. Particles of this size can be produced by nebuliser for continuous administration or by metered-dose inhaler and drug powder inhaler for unit dose medication. For efficient use of the metered-dose inhaler, slow inhalation and actuation must be coordinated. However, efficacy and convenience can be improved when spacer devices are used. Furthermore, spacer devices lessen the oropharyngeal adverse effects of inhaled corticosteroids. Dry powder inhalers are more easily used by children and elderly patients than metered-dose inhalers.

Regardless of the device used, a maximum of 10% of the inhaled dose reaches the airways. The rest of the dose is swallowed and absorbed through the gastrointestinal tract. Most inhaled drugs have low oral bioavailability, either because of a high first-pass metabolism (β2-agonists and glucocorticoids) or because of lack of absorption (sodium cromoglycate). Sulphation of β2-agonists occurs in the wall of the gastrointestinal tract and extensive metabolism of inhaled corticosteroids occurs in the liver. Low bioavailability of the swallowed fraction contributes to reduced adverse effects.

The pharmacokinetic properties of an inhaled drug are of interest. The fraction of the dose absorbed through the lung has the same disposition characteristics as an intravenous dose, and the swallowed fraction has the same disposition as an orally administered dose. However, for many drugs, pharmacokinetic data after inhalation are limited and cannot be used as a criteria for selection of therapy.

Whatever the device used to deliver the aerosolised drug, patients should be instructed on how to use the inhaler device so that maximum benefit may be obtained from their inhaled therapy. Although inhalation therapy is the first-line treatment for asthma, aerosol delivery to the airways and convenience of the devices could be improved, without increasing the cost of therapy.

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  1. Clinical Pharmacy, Hôpital Bicêtre, Paris, France

    Anne-Marie Taburet & Bénédicte Schmit

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  1. Anne-Marie Taburet
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An erratum to this article is available at http://dx.doi.org/10.1007/BF03259524.

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Taburet, AM., Schmit, B. Pharmacokinetic Optimisation of Asthma Treatment. Clin. Pharmacokinet. 26, 396–418 (1994). https://doi.org/10.2165/00003088-199426050-00006

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