title: Evaluation of limited sampling strategies for total and free prednisolone in adult kidney transplant recipients.
abstract: OBJECTIVE
  The aims of this study were to evaluate the predictive performances of all previously derived limited sampling strategies (LSSs) for total prednisolone, and to derive LSSs for free prednisolone in an independent cohort of adult kidney transplant recipients.
  
  
  METHODS
  Total and free prednisolone area under the concentration-time curve profiles from 0 to 12 hours post-dose (AUC(0-12)) were collected from 20 subjects. All previously published total prednisolone LSSs were identified from the literature. Free prednisolone LSSs were developed using multiple linear regression analyses. AUC predicted by each of the LSSs was compared with AUC(0-12). Median percentage prediction error (MPPE) and median absolute percentage prediction error (MAPE) were calculated to evaluate bias and imprecision.
  
  
  RESULTS
  Total dose-adjusted prednisolone exposure varied 5-fold among study participants, while free dose-adjusted prednisolone exposure varied 3-fold. Correlation (r²) between total and free prednisolone AUC(0-12) was 0.79 (p = <0.0001) for the entire study cohort. This correlation was poorer in those early compared with late post-transplant (r² = 0.42 (p = 0.04) versus r² = 0.59 (p = 0.009) respectively). Ten previously published LSSs for total prednisolone and 15 derived LSSs for free prednisolone performed with acceptable levels of bias and imprecision (<15%). Of the free prednisolone LSSs, an equation incorporating 0.25-, 2- and 4-h concentrations showed the highest predictive power (AUC₀-₁₂ = -17.20 + 1.18 × C₀.₂₅ + 2.75 × C₂ + 4.45 × C₄; MPPE = 0.1%, MAPE = 4.6%).
  
  
  CONCLUSIONS
  Wide between-subject variability in drug exposure suggests a role for TDM. LSSs can accurately estimate both total and free prednisolone AUC(0-12). However, given the poor correlation observed between the two parameters, our data suggest that free prednisolone LSSs may be preferable.
authors.affiliation: Department of Nephrology, University of Queensland at the Princess Alexandra Hospital, Level 2, ARTS Building, Ipswich Road, Woolloongabba, Brisbane 4102, QLD, Australia. katherine_barraclough@health.qld.gov.au
authors.forename: Katherine A
authors.initials: KA
authors.lastname: Barraclough
authors.forename: Nicole M
authors.initials: NM
authors.lastname: Isbel
authors.forename: Brett C
authors.initials: BC
authors.lastname: McWhinney
authors.forename: Jacobus P J
authors.initials: JP
authors.lastname: Ungerer
authors.forename: Gregory
authors.initials: G
authors.lastname: Medley
authors.forename: David W
authors.initials: DW
authors.lastname: Johnson
authors.forename: Carmel M
authors.initials: CM
authors.lastname: Hawley
authors.forename: Diana R
authors.initials: DR
authors.lastname: Leary
authors.forename: Scott B
authors.initials: SB
authors.lastname: Campbell
authors.forename: Christine E
authors.initials: CE
authors.lastname: Staatz
mesh_terms: D000328:Adult; D019540:Area Under Curve; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D016030:Kidney Transplantation / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000008:administration & dosage; D011239:Prednisolone / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D016559:Tacrolimus / Q000008:administration & dosage
chemical_list: D007166:Immunosuppressive Agents; D011239:Prednisolone; D009173:Mycophenolic Acid; D016559:Tacrolimus