Monitoring Prednisolone and Prednisone in Saliva

Teeninga, Nynke; Zheng, Guoyan; Freijer, Jan; Ruiter, An F.C.; Ackermans, Mariëtte T.; Holthe, Joana E. Kist-van; Gelder, Teun van; Nauta, Jeroen

doi:10.1097/ftd.0b013e3182899ea2

Cited by 11 publications

(7 citation statements)

References 32 publications

(46 reference statements)

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“…In addition, the free fraction is dose-dependent and exhibits circadian variability (approximately 22% higher in the morning) [74]. The PLN plasma unbound fraction demonstrates a high correlation with the salivary level and a lower correlation with the concentration of the prodrug prednisone (PN) [75,76]. Total and free concentrations of PLN+PN in the OF and plasma display an excellent association [76] (Table 2).…”

Section: Oral Fluids As a Matrix For Therapeutic Drug Monitoringmentioning

confidence: 99%

Alternative Matrices for Therapeutic Drug Monitoring of Immunosuppressive Agents Using LC–MS/MS

Ghareeb

Akhlaghi

2015

Bioanalysis

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Immunosuppressive drugs used in solid organ transplants typically have narrow therapeutic windows and high intra- and intersubject variability. To ensure satisfactory exposure, therapeutic drug monitoring (TDM) plays a pivotal role in any successful posttransplant maintenance therapy. Currently, recommendations for optimum immunosuppressant concentrations are based on blood/plasma measurements. However, they introduce many disadvantages, including poor prediction of allograft survival and toxicity, a weak correlation with drug concentrations at the site of action and the invasive nature of the sample collection. Thus, alternative matrices have been investigated. This paper reviews tandem-mass spectrometry (LC–MS/MS) methods used for the quantification of immunosuppressant drugs utilizing nonconventional matrices, namely oral fluids, fingerprick blood and intracellular and intratissue sampling. The advantages, disadvantages and clinical application of such alternative mediums are discussed. Additionally, sample extraction techniques and basic chromatography information regarding these methods are presented in tabulated form.

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Section: Oral Fluids As a Matrix For Therapeutic Drug Monitoringmentioning

confidence: 99%

Alternative Matrices for Therapeutic Drug Monitoring of Immunosuppressive Agents Using LC–MS/MS

Ghareeb

Akhlaghi

2015

Bioanalysis

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“…Prednisolone is protein bound, and its metabolism is influenced by gender and plasma albumin as well as by liver function and genetic variations in the enzymes CYP3A4, CYP3A5, ABCB1, and NR112 [29]. Repetitive samplings of non-stimulated saliva provide a good estimate of prednisolone turnover in healthy people [29] and in children with nephrotic syndrome [30]. This may allow for individualised dosing of prednisolone to reduce adverse events without compromising efficacy.…”

Section: Background and Rationale {6a}mentioning

confidence: 99%

A randomised controlled unblinded multicentre non-inferiority trial with activated vitamin D and prednisolone treatment in patients with minimal change nephropathy (ADAPTinMCN)

Kristensen

Birn

Ivarsen

2021

Trials

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Background Minimal change nephropathy (MCN) is a common cause of nephrotic syndrome in both adults and children. International guidelines recommend treatment with prednisolone 1 mg/kg/day to adults. This dose is derived from an empirically established dose in children, although children generally attain remission faster and relapse more rapidly than adults. Prednisolone is associated with multiple and serious adverse events. Activated vitamin D has been shown to reduce albuminuria in other glomerular renal diseases with a minimum of adverse events. This study tests the hypothesis that a new treatment regimen in MCN combining reduced dose prednisolone and active vitamin D is as efficient in inducing remission and has fewer and less severe adverse events than standard prednisolone. Furthermore, we aim to establish models allowing for more personalized medicine based on assessment of the individual’s prednisolone metabolism. Methods A randomised controlled multicentre non-inferior unblinded trial including 96 adult, incident patients with biopsy-proven MCN, albuminuria > 3 g/day, and an estimated glomerular filtration rate (eGFR) > 30 ml/min from renal departments in Denmark. Patients are randomised to standard prednisolone (1 mg/kg/day) or reduced prednisolone (0.5 mg/kg/day) and alfacalcidol (0.5 μg/day). The primary outcome is the rate of remissions after 16 weeks and the time from diagnosis to remission. The study will include a saliva test to characterise prednisolone pharmacokinetics and compare them to genetic variations in specific liver enzymes responsible for prednisolone metabolism. Discussion Reducing the prednisolone dose is expected to reduce the number of severe adverse events. This study will examine if reduced prednisolone dose with active vitamin D but without additional immunosuppression is feasible in the treatment of MCN and will reduce the number of adverse events. The findings can potentially change current guidelines for treatment of MCN in adults. Additional outcomes on inter-individual pharmacokinetic and metabolic variations may allow for a more personalised treatment strategy. Trial registration EudraCT 2017-001206-16, ClinicalTrials.gov NCT03210688. Registered on June 3, 2017.

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“…New non-invasive methods such as saliva sampling are far more acceptable for paediatric patients. In a recent adult population PK study, free prednisolone concentrations correlated well with salivary concentrations 11. The same study set-up were later applied in a population PK model in paediatric patients (n=104) with nephrotic syndrome 12.…”

Section: Introductionmentioning

confidence: 99%

Pharmacokinetics of prednisolone in children: an open-label, randomised, two-treatment cross-over trial investigating the bioequivalence of different prednisolone formulations in children with airway disease

Haslund-Krog

Schmidt

Mathôt³

et al. 2019

bmjpo

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IntroductionOne in three Danish children under 3 years of age experience asthma-like symptoms, and one-third will later be diagnosed with asthma. Oral prednisolone is used in various formulations to treat acute asthma. However, the potential differences in bioequivalence between these formulations have never been examined in children despite interchangeable use in clinical practice.Methods and analysisAn open-label, randomised, two-treatment cross-over trial investigating the bioequivalence of different prednisolone formulations in children with airway disease.The included patients (6 months–11 years of age) are admitted to the Department of Paediatric and Adolescent Medicine Nordsjællands University Hospital, Hillerød, with asthma or asthma-like symptoms.The primary objective is to assess the bioequivalence between different prednisolone formulations herein area under the concentration time curve, Cmax and Tmax using saliva samples. The secondary objectives are to evaluate tolerability (five-point face scale), adverse events and severity of the disease. If the patient has an intravenous access for other purposes, the saliva samples will be validated with plasma samples.A total of 66 evaluable patients are needed according to European Medicines Agency Guideline on bioequivalence.Ethics and disseminationTraditional pharmacokinetic trials are burdensome due to the extent of blood samples necessary to capture the time-dependant drug profile. Saliva sampling is far more acceptable for paediatric patients. In addition, this trial adheres to standard dosing strategies. No additional venepunctures are performed, and no additional prednisolone doses are administered.Guidelines for paediatric bioequivalence trials are warranted.Trial registration numberThe Danish Medicines Agency EudraCT: 2017-003590-33, The Ethics Committee case no: H-17027252, and the Danish Data Protection Agency: BFH-2017–103, I-Suite no.: 05935.

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Monitoring Prednisolone and Prednisone in Saliva

Cited by 11 publications

References 32 publications

Alternative Matrices for Therapeutic Drug Monitoring of Immunosuppressive Agents Using LC–MS/MS

Alternative Matrices for Therapeutic Drug Monitoring of Immunosuppressive Agents Using LC–MS/MS

A randomised controlled unblinded multicentre non-inferiority trial with activated vitamin D and prednisolone treatment in patients with minimal change nephropathy (ADAPTinMCN)

Pharmacokinetics of prednisolone in children: an open-label, randomised, two-treatment cross-over trial investigating the bioequivalence of different prednisolone formulations in children with airway disease

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