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.
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Acknowledgements
K Barraclough is currently supported by a National Health and Medical Research Council Medical/Dental Post-graduate Research Scholarship. C Staatz is currently supported by a Lions Medical Research Fellowship. D Johnson is supported by a Queensland Health Research Fellowship. This research is supported by a National Health and Medical Research Council Project Grant, number 511109, and an Amgen-Transplantation Society of Australia and New Zealand Research Grant. The authors would like to thank all the nursing staff of the Department of Nephrology at the Princess Alexandra Hospital for helping with sample collection and Dr Troels Bergmann for his assistance with non-compartmental analysis.
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There was no conflict of interest with regard to any of the authors.
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Barraclough, K.A., Isbel, N.M., McWhinney, B.C. et al. Evaluation of limited sampling strategies for total and free prednisolone in adult kidney transplant recipients. Eur J Clin Pharmacol 67, 1243–1252 (2011). https://doi.org/10.1007/s00228-011-1071-y
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DOI: https://doi.org/10.1007/s00228-011-1071-y