TDM in Psychiatry. First Update of the AGNP Consensus Guidelines

Hiemke, Christoph

doi:10.1055/s-0028-1088254

Cited by 5 publications

(17 citation statements)

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“…Fixing the interindividual variability of Vd could influence the interindividual variability estimates of clearance estimates but in minor extent in consideration of the reported range variability in literature. 37 Second, we have limited data access beyond 12 hours postdose due to the drug being administered twice daily. This could potentially lead to an overestimation of clearance for drugs that distribute to deeper compartments.…”

Section: Discussionmentioning

confidence: 99%

“…First, the limited data during the absorption phase led to the need to fix the absorption rate constant to values reported by others and the interindividual variability for Vd to 0. Fixing the interindividual variability of Vd could influence the interindividual variability estimates of clearance estimates but in minor extent in consideration of the reported range variability in literature 37 . Second, we have limited data access beyond 12 hours postdose due to the drug being administered twice daily.…”

Section: Discussionmentioning

confidence: 99%

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Model‐Informed Precision Dosing Guidance of Ethosuximide Developed from a Randomized Controlled Clinical Trial of Childhood Absence Epilepsy

Mizuno

Capparelli

Fukuda

et al. 2023

Clin Pharma and Therapeutics

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Ethosuximide was identified as the optimal option for new‐onset childhood absence epilepsy (CAE) in a randomized, two‐phase dose escalation comparative effectiveness trial of ethosuximide, lamotrigine, and valproic acid. However, 47% of ethosuximide initial monotherapy participants experienced short‐term treatment failure. This study aimed to characterize the initial monotherapy ethosuximide exposure‐response relationship and to propose model‐informed precision dosing guidance. Dose titration occurred over a 16–20‐week period until patients experienced seizure freedom or intolerable side effects. Subjects with initial monotherapy failure were randomized to one of the other two medications and dose escalation was repeated. A population pharmacokinetic model was created using plasma concentration data (n = 1,320), collected at 4‐week intervals from 211 unique participants during both the initial and second monotherapy phases. A logistic regression analysis was performed on the initial monotherapy cohort (n = 103) with complete exposure‐response data. Eighty‐four participants achieved seizure freedom with a wide range of ethosuximide area under the curves (AUC) ranging from 420 to 2,420 μg·h/mL. AUC exposure estimates for achieving a 50% and 75% probability of seizure freedom were 1,027 and 1,489 μg·h/mL, respectively, whereas the corresponding cumulative frequency of intolerable adverse events was 11% and 16%. Monte Carlo Simulation indicated a daily dose of 40 and 55 mg/kg to achieve 50% and 75% probability of seizure freedom in the overall population, respectively. We identified the need for adjusted mg/kg dosing in different body weight cohorts. This ethosuximide proposed model‐informed precision dosing guidance to achieve seizure freedom carries promise to optimize initial monotherapy success for patients with CAE.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Model‐Informed Precision Dosing Guidance of Ethosuximide Developed from a Randomized Controlled Clinical Trial of Childhood Absence Epilepsy

Mizuno

Capparelli

Fukuda

et al. 2023

Clin Pharma and Therapeutics

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“…7 The constant pharmacokinetic parameters Cl t , F, and f may be taken together to a simple factor to multiply with the 20 dose to yield the lower and upper DRR limits, 7 now called DRC av,ss factors modified from a suggestion in the second update of the TDM consensus guideline. 6 The original publication compiled such factors for 29 psychopharmaca 7 and the first update of the TDM guideline did for 83 psychopharmaca. 5 DRR av,ss is independent of whether D m is applied as a single dose or split into 2 or more equal or unequal partial doses, spread equally or unequally over t, or whether the drug is applied in an immediate-release or a retarded-release formulation.…”

Section: D;cmentioning

confidence: 99%

“…The first update was followed in 2011, 5 and a second update in 2018. 6 In 2008, the dose-related reference range (DRR) was suggested to complement the TRR as a discriminating reference range to identify an individual patient having the following based on his or her individual pharmacokinetic characteristics that deviate from the "normal patient" population pharmacokinetic (DRR as a pharmacokinetic reference range) 7,8 :…”

Section: Introductionmentioning

confidence: 99%

Dose-Related Reference Range as a Tool in Therapeutic Drug Monitoring

Haen

2022

Therapeutic Drug Monitoring

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Background: Therapeutic drug monitoring (TDM) aims to individualize drug therapy. This systematic review provides a state-of-the-art overview of the benefits of adding the dose-related reference range (DRR) as a second reference range to the set of tools used by TDM for measurement and evaluation. It discusses alternative pharmacokinetic approaches for individualization of drug therapy.Methods: Literature was searched in PubMed. Textbooks provided Bateman transformations for calculating expected drug concentrations at various times after drug application in "normal patients," that is, the population of phase II clinical trials. The review compiles conditions and prerequisites for these transformations to be valid.Results: Relating a measured drug concentration to the orienting therapeutic reference range provides pharmacodynamic information for improving the benefit-to-risk ratio of desired drug effects versus adverse drug effects. The discriminating DRR considers a patient's individual pharmacokinetic situation. DRR is statistically based on the pharmacokinetic parameters total clearance, time to reach maximal concentrations, and elimination half-life. Relating the measured drug concentration to a range rather than a particular value, DRR determines if individual patients do or do not belong to the population of "normal patients." Once a patient is identified to be outside the population of "normal patients," the clinical-pharmacological TDM report elaborates the cause. It consists of the measured value, the TDM 9-field-board, the elimination pathways table, and a medication recommendation taking into account clinical information. The internet-based platform KONBEST supports editing of the clinical-pharmacological TDM report. It is personally signed and send to the therapist. Conclusions:The DRR embedded into a clinical-pharmacological TDM report allows adjusting a patient's medication to the patient's individual needs (individualization of drug therapy).

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“…Inconsistent methodologies concerning the way that reference ranges were determined has led to a high variation of ranges reported in the literature. Reported ranges from previous guidelines are more or less considered as experts’ opinions 1 .…”

mentioning

confidence: 99%