High-Dose Methylphenidate and Carboxylesterase 1 Genetic Variability in Patients With Attention-Deficit/Hyperactivity
Andrie C Westerkamp1, Rob Rodrigues Pereira2, Vera R Huitema3
1From the University Center of Psychiatry, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.
Journal of Clinical Psychopharmacology
|October 18, 2023
Summary
High doses of methylphenidate (MPH) in three patients were not explained by genetic variants in the CES1 gene. Further research is needed to understand MPH metabolism and high-dose requirements.
Area of Science:
- Pharmacology
- Genetics
- Neuroscience
Background:
- Methylphenidate (MPH) treats attention-deficit/hyperactivity disorder (ADHD).
- Carboxylesterase 1 (CES1) enzyme metabolizes MPH.
- Some patients require high MPH doses due to pharmacokinetic variations, potentially linked to CES1 gene variants.
Purpose of the Study:
- Investigate the CES1 gene in three patients needing high-dose MPH.
- Determine if CES1 genetic variations explain altered MPH pharmacokinetics.
Main Methods:
- Collected pharmacokinetic (PK) data for three patients on high-dose MPH (180-640 mg).
- Performed PK analysis using a population model, comparing patient data to simulated data.
- Genotyped the CES1 gene for copy number variations and single nucleotide polymorphisms (SNPs) via real-time PCR.
Main Results:
- Patients exhibited lower MPH plasma concentrations than expected for their doses.
- Elimination clearance of MPH was higher in these patients.
- No identified CES1 genetic variations correlated with the observed higher MPH metabolism or clearance.
Conclusions:
- The study did not find a link between known CES1 genetic variants and increased MPH clearance in these three patients.
- The reasons for high-dose MPH requirements in these individuals remain unclear and warrant further investigation.
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