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Prednisolone Concentrations in Plasma (Total and Unbound) and Saliva of Adult Kidney Transplant Recipients

Brooks, Emily MBBS*; Tett, Susan E. PhD; Isbel, Nicole M. PhD*,‡; McWhinney, Brett MPhil, FFSc (RCPA)§; Staatz, Christine E. PhD

doi: 10.1097/FTD.0000000000000687
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Background: Prednisolone displays significant pharmacokinetic variability and exposure–outcome relationships in renal transplant recipients, suggesting a role for drug monitoring in some scenarios. It is highly protein-bound, and the free form is pharmacologically active but cumbersome to measure. Saliva concentrations might reflect free plasma prednisolone and present an alternative measurement. The aim of this study was to examine the correlation between total and free plasma and saliva prednisolone in adult renal transplant recipients.

Methods: Total and free plasma and saliva prednisolone concentrations were measured in 20 patients receiving oral prednisolone 1–2 months after transplant, between pre-dose and 12 hours post-dose. Prednisolone was determined using high-performance liquid chromatography mass spectrometric detection. The Pearson coefficient was used to assess the association between plasma and salivary prednisolone concentrations and area under the concentration–time curves (AUC0–12).

Results: When considering all time points, the total and free plasma prednisolone concentrations correlated well (r2 = 0.81), but there was poor correlation between saliva and free (r2 = 0.003) and total (r2 = 0.01) plasma concentrations. When concentrations before the maximum free prednisolone plasma value were excluded, the correlation between free plasma and saliva concentrations improved (r2 = 0.57). There was a moderate correlation between free and total plasma prednisolone AUC0–12 (r2 = 0.62) using all time points, but a poor correlation between free and total plasma prednisolone AUC0–12 and saliva AUC0–12 (r2 = 0.07; r2 = 0.17).

Conclusions: Total and free plasma prednisolone measurements correlated poorly with saliva measurements; however, correlation improved when concentrations early in the dosing interval were excluded.

*School of Medicine, The University of Queensland, Brisbane, Australia;

School of Pharmacy, The University of Queensland, Brisbane, Australia;

Department of Nephrology, The Princess Alexandra Hospital, Brisbane, Australia; and

§Department of Pathology, Royal Brisbane and Women's Hospital, Brisbane, Australia.

Correspondence: Emily Brooks, MBBS, C/o Associate Professor Christine Staatz, School of Pharmacy, Pharmacy Australia Centre of Excellence, Level 4, 20 Cornwall Street, Woolloongabba, QLD 4102, Australia (e-mail: emily.brooks@health.qld.gov.au).

E. Brooks was a student; S. E. Tett, C. E. Staatz, N. M. Isbel, and B. McWhinney received salaries from University/hospital sources.

E. Brooks performed the literature review, designed the study, collected and analyzed the data, and wrote the first draft of the manuscript. S. E. Tett assisted in the literature review, study design, and manuscript review. N. M. Isbel assisted in the study design, patient recruitment, data collection, and manuscript review. B. McWhinney analyzed the samples and reviewed the manuscript. C. E. Staatz assisted in the literature review, study design, data analysis, and manuscript review.

The authors declare no conflict of interest.

Received April 24, 2019

Accepted June 30, 2019

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