Pharmacokinetic strategies for cyclosporin therapy in organ transplantation

Barry D. Kahan, Maria Welsh, Richard Knight, Stephen Katz, Richard Lewis, Joachim Grevel, Charles T. Van Buren

Research output: Contribution to journalArticlepeer-review

8 Scopus citations

Abstract

Marked interindividual variations in cyclosporin (CsA) produce disparate clinical results in organ transplant recipients. In an attempt to eliminate marked deviations of insufficient or excessive CsA concentrations consequent to the administration of uniform drug doses, test dose pharmacokinetics were performed on each potential organ transplant candidate. An intravenous 3 mg/kg test dose delivered over 3h proved to be readily performed, namely 53% perfect studies, and relatively reliable, namely 73% of observed concentrations within 10% of the predicted values. Furthermore, the use of CsA doses predicted by pretransplant studies reduces the incidence of delayed graft function, early rejection episodes and transplant loss. The oral test dose study predicted a suitable amount of CsA to achieve sufficient gastrointestinal absorption but was less accurate than the iv prediction method: namely, 40% of observed post-transplant concentrations were within 10% of the predicted target value. Furthermore, patients who received oral doses predicted by the test dose strategy showed no improvement in the incidence of acute rejection episodes between 7 and 60 days, and only modestly improved serum creatinine values. The lower accuracy of predictions from oral test dose studies may reflect the impact of non-linear oral (as opposed to iv) drug pharmacokinetics, of variable diet, and/or of altered postoperative gastrointestinal function.

Original languageEnglish (US)
Pages (from-to)333-341
Number of pages9
JournalJournal of Autoimmunity
Volume5
Issue numberSUPPL. A
DOIs
StatePublished - Apr 1992

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Fingerprint Dive into the research topics of 'Pharmacokinetic strategies for cyclosporin therapy in organ transplantation'. Together they form a unique fingerprint.

Cite this