An integrated model for the effect of budesonide on ACTH and cortisol in healthy volunteers

Br J Clin Pharmacol. 2007 Aug;64(2):125-32. doi: 10.1111/j.1365-2125.2007.02867.x. Epub 2007 Mar 1.


Aims: Budesonide, a glucocorticosteroid, is used as a first-line treatment for asthma. The aim of the study was to develop a PK/PD model for the effect of budesonide on ACTH and cortisol.

Methods: The modelling data were generated by conducting a single-blind, randomized, placebo-controlled cross-over study. Ten healthy volunteers inhaled placebo (Placebo Turbohaler) and 1600 microg budesonide (Pulmicort Turbohaler), with a wash-out period of 7 days between treatments. Baseline concentrations of cortisol and ACTH were measured after placebo treatment and concentrations of cortisol, ACTH and budesonide were assessed after budesonide treatment. A one-compartment disposition model was used for budesonide disposition. Based on indirect response models, two types of models, distinguishing between production driven by a sum of cosine functions and production driven by surges, were used in parallel to describe the data.

Results: The surge-based approach was the most appropriate, based on goodness-of-fit, objective function values and number of parameters. The surge-based model that integrated both ACTH and cortisol data was chosen as the final model. The estimated half-lives of endogenous ACTH and cortisol were 9 and 113 min, respectively. The budesonide and ACTH concentrations producing 50% of the maximal response (IC(50) and A(50)) were 0.325 microg l(-1) and 4.96 pmol l(-1).

Conclusions: The present PK/PD model of the effect of budesonide on ACTH and cortisol can serve as a tool for further understanding of the hypothalamic-pituitary-adrenal (HPA) axis and be useful in the development of drugs interacting with the axis.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Adrenocorticotropic Hormone / drug effects*
  • Adult
  • Anti-Asthmatic Agents / administration & dosage
  • Anti-Asthmatic Agents / pharmacokinetics
  • Anti-Asthmatic Agents / pharmacology*
  • Anti-Inflammatory Agents / administration & dosage
  • Anti-Inflammatory Agents / pharmacokinetics
  • Anti-Inflammatory Agents / pharmacology*
  • Budesonide / administration & dosage
  • Budesonide / pharmacokinetics
  • Budesonide / pharmacology*
  • Cross-Over Studies
  • Dose-Response Relationship, Drug
  • Female
  • Humans
  • Male
  • Single-Blind Method
  • Treatment Outcome


  • Anti-Asthmatic Agents
  • Anti-Inflammatory Agents
  • Budesonide
  • Adrenocorticotropic Hormone