ArticleTherapeutic drug monitoring2014
Pharmacokinetics of total and unbound prednisone and prednisolone in stable kidney transplant recipients with diabetes mellitus.
Article in Therapeutic drug monitoring, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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Who cites it
4 citing papers in PubMed, 13 citations in OpenAlex.
- Evaluation of the pharmacokinetics of prednisolone in paediatric patients with acute lymphoblastic leukaemia treated according to Dutch Childhood Oncology Group protocols and its relation to treatment response.British journal of haematology · 2021Trial
- Estimation of Equipotent Doses for Anti-Inflammatory Effects of Prednisolone and AZD9567, an Oral Selective Nonsteroidal Glucocorticoid Receptor Modulator.CPT: pharmacometrics & systems pharmacology · 2020Article
- Urinary prednisolone excretion is a determinant of serum hepcidin levels in renal transplant recipients.American journal of hematology · 2017Article
- Alternative matrices for therapeutic drug monitoring of immunosuppressive agents using LC-MS/MS.Bioanalysis · 2015Review
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundThe corticosteroid prednisone is an important component of posttransplantation immunosuppressive therapy. Pharmacokinetic parameters of prednisone or its pharmacologically active metabolite, prednisolone, are not well characterized in transplant recipients. The objective of this study was to compare the pharmacokinetics of total and unbound prednisone and prednisolone in diabetic and nondiabetic stable kidney transplant recipients and to evaluate the factors influencing plasma protein binding of prednisolone.
methodsPrednisone and prednisolone concentration-time profiles were obtained in 20 diabetic and 18 nondiabetic stable kidney transplant recipients receiving an oral dose of 5-10 mg prednisone per day. In addition to drug and metabolite exposures, factors influencing prednisolone protein binding were evaluated using a nonlinear mixed-effects modeling approach. This model takes into account the binding of prednisolone and cortisol to corticosteroid-binding globulin (CBG) in a saturable fashion and binding of prednisolone to albumin in a nonsaturable fashion. Finally, we have investigated the influence of several covariates including diabetes, glucose concentration, hemoglobin A1c, creatinine clearance, body mass index, gender, age, and time after transplantation on the affinity constant (K) between corticosteroids and their binding proteins.
resultsIn patients with diabetes, the values of dose-normalized area under the concentration-time curves were 27% and 23% higher for total and unbound prednisolone, respectively. Moreover, the ratio of total prednisolone to prednisone concentrations (active/inactive forms) was higher in diabetic subjects (P < 0.001). Modeling protein binding results revealed that the affinity constant of corticosteroid-binding globulin-prednisolone (KCBG,PL) was related to the patient's gender and diabetes status.
conclusionsHigher prednisolone exposure could potentially lead to the increased risk of corticosteroid-related complications in diabetic kidney transplant recipients.
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