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Clinical Pharmacokinetics

, Volume 44, Issue 1, pp 61–98 | Cite as

Pharmacokinetics and Pharmacodynamics of Systemically Administered Glucocorticoids

  • David Czock
  • Frieder KellerEmail author
  • Franz Maximilian Rasche
  • Ulla Häussler
Review Article

Abstract

Glucocorticoids have pleiotropic effects that are used to treat diverse diseases such as asthma, rheumatoid arthritis, systemic lupus erythematosus and acute kidney transplant rejection. The most commonly used systemic glucocorticoids are hydrocortisone, prednisolone, methylprednisolone and dexamethasone. These glucocorticoids have good oral bioavailability and are eliminated mainly by hepatic metabolism and renal excretion of the metabolites. Plasma concentrations follow a biexponential pattern. Two-compartment models are used after intravenous administration, but one-compartment models are sufficient after oral administration.

The effects of glucocorticoids are mediated by genomic and possibly nongenomic mechanisms. Genomic mechanisms include activation of the cytosolic glucocorticoid receptor that leads to activation or repression of protein synthesis, including cytokines, chemokines, inflammatory enzymes and adhesion molecules. Thus, inflammation and immune response mechanisms may be modified. Nongenomic mechanisms might play an additional role in glucocorticoid pulse therapy.

Clinical efficacy depends on glucocorticoid pharmacokinetics and pharmacodynamics. Pharmacokinetic parameters such as the elimination half-life, and pharmacodynamic parameters such as the concentration producing the half-maximal effect, determine the duration and intensity of glucocorticoid effects. The special contribution of either of these can be distinguished with pharmacokinetic/pharmacodynamic analysis. We performed simulations with a pharmacokinetic/pharmacodynamic model using T helper cell counts and endogenous Cortisol as biomarkers for the effects of methylprednisolone. These simulations suggest that the clinical efficacy of low-dose glucocorticoid regimens might be increased with twice-daily glucocorticoid administration.

Keywords

Glucocorticoid Prednisolone Methylprednisolone Glucocorticoid Receptor Diffuse Alveolar Haemorrhage 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

Acknowledgements

This study was supported by the European Commission within the PharmDIS project (BMH4-CT98-9548 and IST Craft-2001-52107). The authors have no conflicts of interest to disclose.

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Copyright information

© Adis Data Information BV 2005

Authors and Affiliations

  • David Czock
    • 1
  • Frieder Keller
    • 1
    Email author
  • Franz Maximilian Rasche
    • 1
  • Ulla Häussler
    • 1
  1. 1.Division of NephrologyUniversity Hospital UlmUlmGermany

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