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2 results on '"pharmacokinetics/pharmacodynamics"'

1. 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.

Author

Sassen SDT, Mathôt RAA, Pieters R, de Haas V, Kaspers GJL, van den Bos C, Tissing WJE, Te Loo DMWW, Bierings MB, van der Sluis IM, and Zwaan CM

Subjects
Adolescent, Antineoplastic Agents, Hormonal therapeutic use, Area Under Curve, Child, Child, Preschool, Female, Humans, Infant, Male, Netherlands epidemiology, Precursor Cell Lymphoblastic Leukemia-Lymphoma blood, Precursor Cell Lymphoblastic Leukemia-Lymphoma epidemiology, Prednisolone therapeutic use, Prospective Studies, Treatment Outcome, Antineoplastic Agents, Hormonal blood, Precursor Cell Lymphoblastic Leukemia-Lymphoma drug therapy, Prednisolone blood
Abstract

Glucocorticoids form the backbone of paediatric acute lymphoblastic leukaemia (ALL) treatment. Many studies have been performed on steroid resistance; however, few studies have addressed the relationship between dose, concentration and clinical response. The aim of the present study was to evaluate the pharmacokinetics of prednisolone in the treatment of paediatric ALL and the correlation with clinical parameters. A total of 1028 bound and unbound prednisolone plasma concentrations were available from 124 children (aged 0-18 years) with newly diagnosed ALL enrolled in the Dutch Childhood Oncology Group studies. A population pharmacokinetic model was developed and post hoc area under the curve (AUC) was tested against treatment outcome parameters. The pharmacokinetics of unbound prednisolone in plasma was best described with allometric scaling and saturable binding to proteins. Plasma protein binding decreased with age. The AUC of unbound prednisolone was not associated with any of the disease parameters or treatment outcomes. Unbound prednisolone plasma concentrations correlated with age. No effect of exposure on clinical treatment outcome parameters was observed and does not substantiate individualised dosing. Poor responders, high-risk and relapsed patients showed a trend towards lower exposure compared to good responders. However, the group of poor responders was small and requires further research., (© 2021 The Authors. British Journal of Haematology published by British Society for Haematology and John Wiley & Sons Ltd.)

Published
2021
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2. Severe COVID-19 in a renal transplant recipient: A focus on pharmacokinetics.

Author

Meziyerh S, Zwart TC, van Etten RW, Janson JA, van Gelder T, Alwayn IPJ, de Fijter JW, Reinders MEJ, Moes DJAR, and de Vries APJ

Subjects
Adult, Antiviral Agents administration & dosage, Antiviral Agents pharmacokinetics, Betacoronavirus, COVID-19, Chloroquine administration & dosage, Chloroquine pharmacokinetics, Drug Combinations, Drug Interactions, Everolimus administration & dosage, Humans, Immunocompromised Host, Immunosuppressive Agents administration & dosage, Immunosuppressive Agents pharmacokinetics, Kidney Failure, Chronic surgery, Lopinavir administration & dosage, Lopinavir pharmacokinetics, Male, Netherlands, Pandemics, Radiography, Thoracic, Ritonavir administration & dosage, Ritonavir pharmacokinetics, SARS-CoV-2, Treatment Outcome, Coronavirus Infections complications, Coronavirus Infections therapy, Everolimus pharmacokinetics, Kidney Failure, Chronic complications, Kidney Transplantation, Pneumonia, Viral complications, Pneumonia, Viral therapy, Transplant Recipients
Abstract

The current coronavirus disease 2019 (COVID-19) pandemic requires extra attention for immunocompromised patients, including solid organ transplant recipients. We report on a case of a 35-year-old renal transplant recipient who suffered from a severe COVID-19 pneumonia. The clinical course was complicated by extreme overexposure to the mammalian target of rapamycin inhibitor everolimus, following coadministration of chloroquine and lopinavir/ritonavir therapy. The case is illustrative for dilemmas that transplant professionals may face in the absence of evidence-based COVID-19 therapy and concurrent pressure for exploration of experimental pharmacological treatment options. However, the risk-benefit balance of experimental or off-label therapy may be weighed differently in organ transplant recipients than in otherwise healthy COVID-19 patients, owing to their immunocompromised status and potential drug interactions with immunosuppressive therapy. With this case report, we aimed to achieve increased awareness and improved management of drug-drug interactions associated with the various treatment options for COVID-19 in renal transplant patients., (© 2020 The Authors. American Journal of Transplantation published by Wiley Periodicals LLC on behalf of The American Society of Transplantation and the American Society of Transplant Surgeons.)

Published
2020
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