Exploratory Study of Total and Free Prednisolone Plasma Exposure and Cushingoid Appearance, Quality of Life and Biochemical Toxicity in Adult Male Kidney Transplant Recipients
Article
Article Title | Exploratory Study of Total and Free Prednisolone Plasma Exposure and Cushingoid Appearance, Quality of Life and Biochemical Toxicity in Adult Male Kidney Transplant Recipients |
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ERA Journal ID | 14716 |
Article Category | Article |
Authors | Bergmann, Troels K., Isbel, Nicole M., Ostini, Remo, Barraclough, Katherine A., Campbell, Scott B., McWhinney, Brett C., Inder, Warrick J., Russell, Anthony and Staatz, Christine E. |
Journal Title | Clinical Drug Investigation |
Journal Citation | 35 (11), pp. 743-750 |
Number of Pages | 9 |
Year | Nov 2015 |
Place of Publication | United Kingdom |
ISSN | 1173-2563 |
Digital Object Identifier (DOI) | https://doi.org/10.1007/s40261-015-0334-2 |
Web Address (URL) | https://link.springer.com/article/10.1007/s40261-015-0334-2 |
Abstract | Background and Objective: Long-term adverse effects of oral glucocorticoids are frequent and serious. Large between-patient variability in the pharmacokinetics of prednisolone might explain why drug dose is a poor predictor of drug-related toxicity. The aim of the study was to investigate relationships between prednisolone exposure and adverse effects. Methods: Male kidney transplant recipients were recruited for serial blood sampling and assessment of glucocorticoid-related adverse effects including dyslipidaemia, abnormal body fat distribution, Cushingoid appearance and impaired quality of life. Total and free prednisolone plasma concentrations were determined using ultra-high-performance liquid chromatography with tandem mass spectrometric detection. Prednisolone exposure was estimated using a limited sampling strategy. Results: Fifty-six patients were recruited. Patients had a mean age of 54 years and median time post-transplantation of 75 months. Median prednisolone dose was 5 mg. Mean area under the plasma concentration–time curve was 2390 nmol h/L (±580) (SD) and 175 nmol h/L (±78) for total and free prednisolone, respectively. Waist to upper arm circumference ratio was positively associated with free prednisolone plasma exposure with a Spearman correlation coefficient of 0.30 (p value 0.02). The correlation coefficient was 0.24 (p value 0.08) for neck to upper arm circumference ratio and free prednisolone plasma exposure. The clinical Cushingoid phenotype as determined by the Visual Assessment of Cushing’s Severity (VACS) score was associated with a reduced score relating to physical functioning on the SF-12, but there was no significant relationship between free prednisolone plasma exposure and quality-of-life scores. Lipid levels and haemoglobin A1c (HbA1c) were not associated with total or free prednisolone exposure. Conclusions: There is a positive correlation between free prednisolone plasma exposure and waist to upper arm circumference ratio in adult male kidney transplant recipients on low maintenance prednisolone doses. There is no significant association between total or free prednisolone plasma exposure and plasma glucose and lipid levels in the low prednisolone dose range. |
Keywords | Adult; Aged; Body Fat Distribution; Chromatography, High Pressure Liquid; Cushing Syndrome; Female; Hemoglobin A, Glycosylated; Humans; Kidney Transplantation; Lipids; Male; Middle Aged; Prednisolone; Prospective Studies; Quality of Life; Tandem Mass Spectrometry |
Public Notes | Files associated with this item cannot be displayed due to copyright restrictions. |
Byline Affiliations | University of Queensland |
Odense University Hospital, Denmark | |
Department of Health, Victoria | |
Department of Health, Queensland |
https://research.usq.edu.au/item/wv30x/exploratory-study-of-total-and-free-prednisolone-plasma-exposure-and-cushingoid-appearance-quality-of-life-and-biochemical-toxicity-in-adult-male-kidney-transplant-recipients
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