title: A practical limited sampling strategy to predict free prednisolone exposure and glycemia in kidney transplant recipients.
abstract: BACKGROUND
  Despite significant interindividual variability in prednisolone pharmacokinetics and potentially serious consequences with inadequate or excessive exposure, monitoring of prednisolone levels is not employed to guide therapy. As ultrahigh-performance liquid chromatography-tandem mass spectrometry methods can now measure the active free fraction of prednisolone, this study aimed to evaluate the performance of 15 published limited sampling strategies (LSSs) for predicting free prednisolone exposure in adult kidney transplant recipients and to examine the relationship between free/total prednisolone exposure and plasma glucose.
  
  
  METHODS
  The study was performed in 11 subjects without diabetes 3-4 weeks postkidney transplantation. Area under the concentration time curve profiles of total and free prednisolone from 0 to 12 hours postdose (AUC₀₋₁₂) were determined and compared with predicted AUC₀₋₁₂ values calculated from published LSSs. Venous glucose was measured concurrently with the 13 sampling time points.
  
  
  RESULTS
  The mean (±SD) age of subjects was 52 ± 12 years, 5 were men and the median (interquartile range) daily prednisolone dose was 20.0 mg (20.0-22.5). Interindividual variation in dose-adjusted free and total prednisolone exposure was 1.9- and 3.2-fold, respectively. All 15 free prednisolone LSSs exhibited good correlation (r ≥ 0.83), with bias and imprecision less than 15%. An LSS incorporating 1.25- and 3-hour samples had the highest predictive power (r = 0.97, bias 1.2%, imprecision 5.6%). Free prednisolone AUC₀₋₁₂ correlated with peak glucose levels (r = 0.65, P = 0.037), as did predicted AUC₀₋₁₂ from 14/15 LSSs.
  
  
  CONCLUSIONS
  Biologically active free prednisolone exposure can be accurately predicted postkidney transplantation by LSSs incorporating 2-point concentration sampling. Peak plasma glucose concentration correlated well with prednisolone exposure.
authors: *Department of Medicine, Royal Melbourne Hospital, University of Melbourne, Parkville, Victoria, Australia; †Department of Diabetes and Endocrinology, Royal Melbourne Hospital, Parkville, Victoria, Australia; ‡Department of Nephrology, University of Queensland at the Princess Alexandra Hospital, Brisbane, Queensland, Australia; §Department of Chemical Pathology, Pathology Queensland, Royal Brisbane and Women's Hospital, Brisbane, Queensland, Australia; Departments of ¶Chemical Pathology, and ‖Nephrology, Royal Melbourne Hospital, Parkville, Victoria, Australia; and #Department of Medicine, NorthWest Academic Centre, University of Melbourne, St Albans, Victoria, Australia.
authors: Christopher J
authors: CJ
authors: Yates
authors: Katherine A
authors: KA
authors: Barraclough
authors: Brett C
authors: BC
authors: McWhinney
authors: Jacobus P J
authors: JP
authors: Ungerer
authors: Robert O
authors: RO
authors: Fullinfaw
authors: Peter G
authors: PG
authors: Colman
authors: Spiros
authors: S
authors: Fourlanos
authors: Solomon J
authors: SJ
authors: Cohney
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D019540:Area Under Curve; D001786:Blood Glucose / Q000187:drug effects; D001800:Blood Specimen Collection; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D016903:Drug Monitoring / Q000379:methods*; D005260:Female; D005938:Glucocorticoids / Q000008:administration & dosage / Q000493:pharmacokinetics*; D006801:Humans; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D011239:Prednisolone / Q000008:administration & dosage / Q000493:pharmacokinetics*; D013048:Specimen Handling; D053719:Tandem Mass Spectrometry / Q000379:methods; D013997:Time Factors; D055815:Young Adult
chemical_list: D001786:Blood Glucose; D005938:Glucocorticoids; D011239:Prednisolone