TDM in psychiatry and neurology: A comprehensive summary of the consensus guidelines for therapeutic drug monitoring in neuropsychopharmacology, update 2017; a tool for clinicians

Schoretsanitis, Georgios; Paulzen, Michael; Unterecker, Stefan; Schwarz, Markus J.; Conca, Andreas; Zernig, Gerald; Gründer, Gerhard; Haen, E; Baumann, Pierre; Bergemann, Niels; Clement, Hans Willi; Domschke, Katharina; Eckermann, Gabriel; Egberts, Karin; Gerlach, Manfred; Greiner, Christine; Havemann-Reinecke, Ursula; Hefner, Gudrun; Helmer, Renate; Janssen, G. M. E.; Jaquenoud-Sirot, E.; Laux, Gerd; Messer, Thomas; Mößner, Rainald; Müller, Matthias J.; Pfuhlmann, Bruno; Riederer, Peter; Saria, Alois; Schoppek, Bernd; Gracia, Margarete Silva; Stegmann, Benedikt; Steimer, Werner; Stingl, Julia C.; Uhr, Manfred; Ulrich, S.; Waschgler, Roland; Zurek, Gabriela; Hiemke, Christoph

doi:10.1080/15622975.2018.1439595

Cited by 110 publications

(85 citation statements)

References 23 publications

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“…In addition, recommendations for TDM have been expressed about hundreds of therapeutic agents, e.g. anticancer drugs (Widmer et al, 2014), biologics (Imamura, 2019), antiretrovirals (Punyawudho et al, 2016), antiinfectives (Muller et al, 2018), psychotropic agents (Schoretsanitis et al, 2018) etc. If such measurements are to become largely available in routine medical practice, traditional empiricism will not suffice anymore to support the clinical interpretation of drug concentration results by practitioners.…”

Section: Introductionmentioning

confidence: 99%

The Steps to Therapeutic Drug Monitoring: A Structured Approach Illustrated With Imatinib

et al. 2020

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Pharmacometric methods have hugely benefited from progress in analytical and computer sciences during the past decades, and play nowadays a central role in the clinical development of new medicinal drugs. It is time that these methods translate into patient care through therapeutic drug monitoring (TDM), due to become a mainstay of precision medicine no less than genomic approaches to control variability in drug response and improve the efficacy and safety of treatments. In this review, we make the case for structuring TDM development along five generic questions: 1) Is the concerned drug a candidate to TDM? 2) What is the normal range for the drug's concentration? 3) What is the therapeutic target for the drug's concentration? 4) How to adjust the dosage of the drug to drive concentrations close to target? 5) Does evidence support the usefulness of TDM for this drug? We exemplify this approach through an overview of our development of the TDM of imatinib, the very first targeted anticancer agent. We express our position that a similar story shall apply to other drugs in this class, as well as to a wide range of treatments critical for the control of various life-threatening conditions. Despite hurdles that still jeopardize progress in TDM, there is no doubt that upcoming technological advances will shape and foster many innovative therapeutic monitoring methods.

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Section: Introductionmentioning

confidence: 99%

The Steps to Therapeutic Drug Monitoring: A Structured Approach Illustrated With Imatinib

et al. 2020

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“…The significant interindividual differences in plasma concentrations after similar doses of methylphenidate indicate that the dosage should be individually titrated for optimal effect and to avoid toxicity [6]. The monitoring of methylphenidate concentrations is usually based on non-enantioselective methods [12]. However, as the d-threo-enantiomer is considered to be pharmacologically more active than the l-threo-enantiomer [13,14], the determination of enantiomer concentrations could be crucial.…”

Section: Introductionmentioning

confidence: 99%

Pharmacokinetics of methylphenidate and ritalinic acid in plasma correlations with exhaled breath and oral fluid in healthy volunteers

Arvidsson

Beck

Ackehed

et al. 2019

Eur J Clin Pharmacol

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Purpose The primary aim of this study was to explore the potential of alternative sampling matrices for methylphenidate by assessing the correlations between dl-threo-methylphenidate and dl-threo-ritalinic acid concentrations in exhaled breath and oral fluid with those in plasma, in repeated samples collected after a single oral dose of methylphenidate. The secondary aim was to study the enantioselective pharmacokinetics of methylphenidate in plasma, with a focus on interindividual variability in the metabolism of methylphenidate to ritalinic acid. Methods Twelve healthy volunteers received a single oral dose of dl-threo-methylphenidate (Ritalin® capsules, 20 mg). Venous blood samples were collected for 24 h, and plasma analyzed for threo-enantiomers of methylphenidate and ritalinic acid with LC-MS/MS. Repeated sampling of exhaled breath, using a particle filter device, and of non-stimulated oral fluid, using a felt pad device, was also performed. Exhaled breath and oral fluid were analyzed with a non-enantioselective LC-MS/MS method for dlthreo-methylphenidate and dl-threo-ritalinic acid. Results In all subjects, d-threo-methylphenidate was detectable in plasma for at least 15 h after the dose with a biphasic profile. lthreo-Methylphenidate was measurable in only five subjects and in most cases in low concentrations. However, one female subject displayed a biphasic concentration-time profile for l-threo-methylphenidate. This subject also had the highest d-threo-methylphenidate AUC (191 ng*h/mL versus 32-119 ng*h/mL in the other subjects). d-threo-Ritalinic acid concentrations were on average 25-fold higher (range 6-126) than the corresponding d-threo-methylphenidate concentrations. Single-time point plasma concentration ratios between d-threo-ritalinic acid and d-threo-methylphenidate 1.5-12 h after dose correlated highly (r = 0.88-0.98) with the d-threo-ritalinic acid AUC/d-threo-methylphenidate AUC ratio. In eleven subjects, dl-threo-methylphenidate in oral fluid mirrored the biphasic profile of methylphenidate (sum of dand l-threo-enantiomers) in plasma, but the concentrations in oral fluid were on average 1.8 times higher than in plasma. dl-threo-Methylphenidate was detected in exhaled breath in all subjects, but there was no consistent concentration-time pattern. Conclusions In some subjects, the pharmacologically less active l-threo-enantiomer may contribute to the total plasma methylphenidate concentrations. Monitoring methylphenidate concentrations without enantiomeric determination carries the risk of missing such subjects, which might affect how the plasma concentrations of methylphenidate are interpreted and used for clinical decision making. The use of exhaled breath and oral fluid to assess medication adherence to MPH in patients with ADHD warrants further studies.

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“…Nevertheless, the recently published literature on the t 1/2 of LAI antipsychotics appears quite limited; due to space limitations we are going to demonstrate this with 2 examples: 1) limited knowledge of the t 1/2 of LAI paliperidone, and 2) unawareness of the concept of t 1/2 in a published case of LAI risperidone TDM. Regarding the t 1/2 of once-a-month LAI paliperidone (PP1M), the AGNP guideline provides a range of 25-49 days [3], which appears wide to us, although we suspect that its upper range may not be high enough. If we assume that 5 half-lives [5] provides time to eliminate over 95 % of a drug concentration after reaching steady state, it suggests that after 245 (5 × 49 = 245) days, or less than 9 months, one should not detect any paliperidone levels after the last PP1M injection, but in one case detectable blood levels were reported in a patient after 19 months [6].…”

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confidence: 83%

“…As long-acting injectable (LAI) antipsychotics account for increasing prescription rates in clinical practice [1], there is great need to enhance their safety and efficacy. Due to lack of data, the third and latest version of the Arbeitsgemeinschaft für Neuropsychopharmakologie und Pharmakopsychiatrie (AGNP) Consensus Guidelines for therapeutic drug monitoring (TDM) in psychiatry and neurology adopted the reference ranges of the oral formulations for the LAI medications [2,3]. This option is far from ideal [4].…”

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confidence: 99%

Studies of Half-Lives of Long-Acting Antipsychotics are Needed

2018

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TDM in psychiatry and neurology: A comprehensive summary of the consensus guidelines for therapeutic drug monitoring in neuropsychopharmacology, update 2017; a tool for clinicians

Abstract: The present guidelines for TDM application for neuropsychiatric agents aim to assist clinicians in enhancing safety and efficacy of treatment.

Cited by 110 publications

References 23 publications

The Steps to Therapeutic Drug Monitoring: A Structured Approach Illustrated With Imatinib

The Steps to Therapeutic Drug Monitoring: A Structured Approach Illustrated With Imatinib

Pharmacokinetics of methylphenidate and ritalinic acid in plasma correlations with exhaled breath and oral fluid in healthy volunteers

Studies of Half-Lives of Long-Acting Antipsychotics are Needed

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