title: The pharmacokinetics of prednisolone and prednisone in adult liver transplant recipients early after transplantation.
abstract: BACKGROUND
  Glucocorticoids represent a cornerstone in the immunosuppressive therapy after solid organ transplantation. Interconversion between active and inactive states of glucocorticoids (ie, prednisolone and prednisone) is catalyzed by the enzymes 11β-hydroxysteroid dehydrogenases 1 and 2.
  
  
  METHODS
  This study investigated the pharmacokinetics of prednisolone and prednisone in 16 liver transplant recipients. Blood samples were collected in four 12-hour dosing intervals during the first 3 weeks posttransplant, including samples drawn at 13 time points.
  
  
  RESULTS
  Area under the time-concentration curve of prednisolone was 3-13 μg·h·mL·mg·kg with maximum concentrations (Cmax) between 0.37 and 2.5 μg·mL·mg·kg and trough concentrations (C0) between 0.13 and 1.1 μg·mL·mg·kg. The elimination half-lives were 1.9-10.3 hours. Apparent volume of distribution (VD/F) and apparent clearance (Cl/F) were 23-159 L and 4.7-28.7 L/h, respectively.
  
  
  CONCLUSIONS
  This study demonstrated large intraindividual and interindividual variabilities in glucocorticoid pharmacokinetics. The results suggest that current prednisolone dosing early after liver transplantation might be too high, in particular when coadministered with methylprednisolone. These findings indicate a potential for improvement by personalized dosing of glucocorticoids in organ transplantation.
authors: Department of Medical Biochemistry, Oslo University Hospital, Oslo, Norway.
authors: Ingjerd
authors: I
authors: Sæves
authors: Pål-Dag
authors: PD
authors: Line
authors: Stein
authors: S
authors: Bergan
mesh_terms: D000328:Adult; D000368:Aged; D019540:Area Under Curve; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000097:blood / Q000493:pharmacokinetics*; D008099:Liver / Q000378:metabolism*; D016031:Liver Transplantation; D008297:Male; D008875:Middle Aged; D011239:Prednisolone / Q000097:blood / Q000493:pharmacokinetics*; D011241:Prednisone / Q000097:blood / Q000493:pharmacokinetics*; D055815:Young Adult
chemical_list: D007166:Immunosuppressive Agents; D011239:Prednisolone; D011241:Prednisone