Pharmacokinetics of inhaled drugs

Br J Clin Pharmacol. 1996 Dec;42(6):697-705. doi: 10.1046/j.1365-2125.1996.00493.x.

Abstract

1. A high therapeutic ratio for the inhaled route of administration is achieved by delivering doses which achieve a high local concentration in the lung and relatively low levels of systemic absorption. 2. Pharmacokinetic evaluation of drug absorption from the lungs provides an accurate and reproducible method for comparing different inhaler delivery systems, as well as for evaluating bioequivalence of generic drug formulations. 3. The measurement of drug absorption from the lungs may also be applied to assess the effects of inhalation technique on drug delivery in vivo. For example with salbutamol delivered via a large volume spacer, lung bioavailability has been shown to be altered by factors such as the number of actuated puffs, inhalation-actuation delay and washing procedure. 4. Differences in drug delivery to the lungs between dry powder reservoir and pressurised metered-dose aerosol devices translate directly into commensurate differences in clinical efficacy for delivery of both inhaled beta 2-adrenoceptor agonists and corticosteroids. 5. For inhaled corticosteroids, pharmacokinetic evaluation using oral charcoal to obviate alimentary absorption may be applied to quantify the relative gut and lung components of systemic bioavailability. In tandem with information on receptor potency and affinity, drug elimination and distribution, these data may help in part to explain observed differences between different inhaled corticosteroids in terms of their systemic bioactivity profiles. 6. Studies are required to evaluate whether pharmacokinetic evaluation of lung absorption is a suitable way of quantifying delivery of nebulised aminoglycoside antibiotics, as for example in patients with cystic fibrosis. 7. Pharmacokinetic evaluation appears to have an established role in the quantification of drug delivery to the lungs and provides important information which is complimentary to other techniques such as radiolabelled deposition. The next decade of research into pharmacokinetics of established and novel drugs and delivery systems is awaited with keen interest, and will hopefully provide a greater understanding into ways of optimising the benefit-risk ratio for inhaled drugs.

Publication types

  • Review

MeSH terms

  • Administration, Inhalation*
  • Biological Availability
  • Humans
  • Lung / metabolism*
  • Pharmacokinetics*