Evaluation of limited sampling strategies for total and free prednisolone in adult kidney transplant recipients

Barraclough, Katherine A, Isbel, Nicole M., McWhinney, Brett C., Ungerer, Jacobus P. J., Medley, Gregory, Johnson, David W., Hawley, Carmel M., Leary, Diana R., Campbell, Scott B. and Staatz, Christine E. (2011) Evaluation of limited sampling strategies for total and free prednisolone in adult kidney transplant recipients. European Journal of Clinical Pharmacology, 67 12: 1243-1252. doi:10.1007/s00228-011-1071-y

Author Barraclough, Katherine A
Isbel, Nicole M.
McWhinney, Brett C.
Ungerer, Jacobus P. J.
Medley, Gregory
Johnson, David W.
Hawley, Carmel M.
Leary, Diana R.
Campbell, Scott B.
Staatz, Christine E.
Title Evaluation of limited sampling strategies for total and free prednisolone in adult kidney transplant recipients
Journal name European Journal of Clinical Pharmacology   Check publisher's open access policy
ISSN 0031-6970
Publication date 2011-12
Sub-type Article (original research)
DOI 10.1007/s00228-011-1071-y
Volume 67
Issue 12
Start page 1243
End page 1252
Total pages 10
Place of publication Heidelberg, Germany
Publisher Springer
Collection year 2012
Language eng
Formatted abstract
Purpose: 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 (AUC0-12) 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 AUC0-12. 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 AUC0-12 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 AUC0-12. However, given the poor correlation observed between the two parameters, our data suggest that free prednisolone LSSs may be preferable.
Keyword Area under the concentration-time curve
Limited sampling strategies
Therapeutic drug monitoring
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2012 Collection
School of Medicine Publications
School of Pharmacy Publications
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Created: Wed, 28 Sep 2011, 15:47:12 EST by Charna Kovacevic on behalf of School of Pharmacy