Public Defence: Ragnhild Kristine Heier Skauby Ragnhild Kristine Heier Skauby at Institute of Clinical Medicine will be defending the thesis “Prednisolone and prednisone pharmacokinetics in renal transplant recipients” for the degree of PhD (Philosophiae Doctor).

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Photo: Ingebjørg Berdal

Due to copyright reasons, an electronic copy of the thesis must be ordered from the faculty. In order for the faculty to have time to process the order, it must be received by the faculty no later than 2 days prior to the public defence. Orders received later than 2 days before the defence will not be processed. Inquiries regarding the thesis after the public defence must be addressed to the candidate.

Trial Lecture – time and place

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Adjudication committee

  • First opponent: Assistant Professor Dirk Jan R. Moes, Leiden University Medical Center, The Netherlands
  • Second opponent: Professor II Marit Dahl Solbu, The Arctic University of Norway (UiT)
  • Third member and chair of the evaluation committee: Professor II Kirsten Muri Boberg, University of Oslo

Chair of the Defence

Professor II Trond Geir Jenssen, University of Oslo

Principal Supervisor

Professor II Stein Bergan, University of Oslo


The main findings of this study was the large variability in prednisolone and prednisone plasma concentrations between patients, even after adjusting for dose and bodyweight.

Glucocorticoids remain cornerstones in immunosuppressive therapy, but are associated with a wide range of unwanted side effects. In renal transplant recipients, dosing of glucocorticoids is based on clinical assessments. Whether therapeutic drug monitoring of prednisolone is able to improve clinical outcomes is unknown.  This doctoral thesis aimed to investigate the pharmacokinetics of prednisolone and prednisone in renal transplant recipients, and to identify the need and feasibility for individualizing the dosing of prednisolone.

We obtained blood samples covering a 7, 12 or 24-hour concentration-time profile from both a pediatric and an adult population receiving peroral prednisolone. The blood samples were analyzed for total concentrations of prednisolone, prednisone, cortisol and cortisone, using mass spectrometry. In an in vitro incubation study applying a substrate depletion approach, the intrinsic clearance of prednisolone in recombinant CYP3A4 and CYP3A5 enzymes was determined.

In addition to the large variability in kinetics between patients, we found a higher exposure of prednisolone and a higher ratio of prednisolone/prednisone in patients receiving concurrent i.v. methylprednisolone, in adults compared with children and in three pediatric patients with post-transplant diabetes mellitus. An algorithm based on three sampling points: pre-dose plus two and four hours after prednisolone dosing, predicted prednisolone AUC0-24 in adults well. The results from the in vitro study indicated that prednisolone is metabolized by rCYP3A4 rather than rCYP3A5.

The papers in this thesis have emphasized the need for improvements in prednisolone dosing regimens, and indicate that a more moderate dosing of prednisolone without compromising efficacy may be possible. Based on these results, we suggest to develop strategies for individualizing and optimizing prednisolone therapy.

Additional information

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Published Jan. 21, 2022 1:27 PM - Last modified Feb. 4, 2022 11:53 AM