Pharmacokinetics of Modified-Release Prednisone Tablets in Healthy Subjects and Patients With Rheumatoid Arthritis

Hartmut Derendorf, Klaus Ruebsamen, Lynsey Clarke, Achim Schaeffler, John R Kirwan

Research output: Contribution to journalArticle (Academic Journal)peer-review

17 Citations (Scopus)
813 Downloads (Pure)

Abstract

In rheumatoid arthritis (RA), nocturnal release of proinflammatory cytokines is not adequately counteracted by endogenous glucocorticoid and is associated with symptoms of morning stiffness and pain. Taking exogenous glucocorticoid during the night reduces morning stiffness significantly more than treatment at the conventional time in the morning, although waking to take tablets is unacceptable for patients. Modified-release prednisone tablets were developed to allow administration at bedtime for programmed delivery of glucocorticoid during the night. Single-center crossover studies were conducted, each in ≤24 healthy subjects, to compare the pharmacokinetics of a single 5-mg oral dose of modified-release prednisone and conventional prednisone, as well as the effect of food on bioavailability. There was no substantial difference in pharmacokinetic parameters of the formulations apart from the programmed delay in release of glucocorticoid from the modified-release tablets (C(max) 97%, AUC(0-∞) 101%, 90% confidence intervals within the requisite range for bioequivalence). Administration after a full or light meal did not affect pharmacokinetic characteristics, but bioavailability was reduced under fasted conditions. Pharmacokinetic evaluation in 9 patients with RA confirmed that modified-release prednisone tablets taken at bedtime (around 22:00 h) with or after an evening meal result in programmed release of glucocorticoid 4 to 6 hours after intake.
Original languageEnglish
Pages (from-to)326-33
Number of pages8
JournalJournal of Clinical Pharmacology
Volume53
Issue number3
Early online date24 Jan 2013
DOIs
Publication statusPublished - 27 Feb 2013

Bibliographical note

© The Author(s) 2013.

Keywords

  • modifi ed-release prednisone
  • pharmacokinetics
  • bioavailability
  • rheumatoid arthritis

Fingerprint Dive into the research topics of 'Pharmacokinetics of Modified-Release Prednisone Tablets in Healthy Subjects and Patients With Rheumatoid Arthritis'. Together they form a unique fingerprint.

Cite this