The study team will determine the association between d,l-methylphenidate (MPH) therapeutic outcomes in ADHD patients and genetic variants of CES1 and reveal key associations between CES1 genotypes and the PK and PD of MPH.
Name: Methylphenidate
Description: study to determine doseType: DrugMethylphenidate
Description: The maximum plasma concentration achieved after dosing.
Measure: Maximum methylphenidate plasma concentration (Cmax), Time: up to 8 HoursDescription: The time after administration of a drug when the maximum plasma concentration is reached; when the rate of absorption equals the rate of elimination.
Measure: Time to maximum concentration (Tmax) Time: up 8 hoursDescription: Area under the plasma concentration-time curve from time zero to the last measurable concentration.
Measure: Area under the plasma concentration curve (AUClast) Time: up to 8 hoursDescription: Area under the plasma concentration-time curve from time zero to infinity.
Measure: Area under the plasma concentration curve (AUCinf) Time: up to 8 hoursSingle Group Assignment
There are 2 SNPs
In addition, the study team's in vitro studies have revealed that another common CES1 variant D203E (rs2307227) exhibited significantly impaired activity on MPH metabolism, although the effects on D203E on clinical response are in need of further elucidation. --- D203E ---
In addition, the study team's in vitro studies have revealed that another common CES1 variant D203E (rs2307227) exhibited significantly impaired activity on MPH metabolism, although the effects on D203E on clinical response are in need of further elucidation. --- D203E --- --- D203E ---
The study team's hypothesis is that the CES1 variants, such as the G143E and D203E, can significantly alter the expression and/or activity of CES1, thereby influencing the metabolism and disposition of MPH. --- G143E --- --- D203E ---
The first clinically significant CES1 variant G143E (rs71647871), discovered in the study team's lab during the course of a healthy volunteer MPH PK study, led to gross impairments in MPH metabolism. --- G143E ---
The study team has established the minor allele frequency (MAF) of the G143E variant as 3-4% in the general population. --- G143E ---
G143E carrier's frequency 6-8%) with a genetically impaired ability to metabolize/deactivate the drug will receive it - exposing them to high systemic concentrations of MPH and any attendant risks or toxicities. --- G143E ---
The study team's hypothesis is that the CES1 variants, such as the G143E and D203E, can significantly alter the expression and/or activity of CES1, thereby influencing the metabolism and disposition of MPH. --- G143E ---