Metabolism of Methylphenidate and Enalapril Based on CES1 Genotype

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to determine whether differences in the gene coding for the liver enzyme carboxylesterase 1 (CES1) means differences in the metabolism of two CES1 dependent drugs, enalapril and methylphenidate.

Official Title
-----------------
Metabolism of Methylphenidate and Enalapril Based on CES1 Genotype

Conditions
-----------------
Carboxylesterase 1 (CES1) Genotype, CES1 Activity

Intervention / Treatment
-----------------
* Drug: Methylphenidate
* Drug: Enalapril


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: > 18 years old Caucasian Exclusion Criteria: Chronic disease (except hay fever and eczema) Pregnancy Smoking High level of alcohol consumption (> 21 units per week for men and 14 for women) Known allergy towards methylphenidate and enalapril Permanent use of medication (contraception ok)

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Basic Science
Allocation: Non-Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Methylphenidate<br> | Drug: Methylphenidate<br>* 10 mg as a single dose followed by blood samples for the next 33 hours<br>* Other names: Ritalin;|
| Experimental: Enalapril<br> | Drug: Enalapril<br>* 10 mg as a single dose followed by blood samples for the next 72 hours<br>* Other names: Corodil;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Peak plasma concentration (Cmax) of methylphenidate |  | Predose, ½, 1, 1½, 2, 2½, 3, 4, 6, 8, 10, 24 and 33 hours post-dose | 
| Time to peak plasma concentration (Tmax) of methylphenidate |  | Predose, ½, 1, 1½, 2, 2½, 3, 4, 6, 8, 10, 24 and 33 hours post-dose | 
| Terminal half life (t½) of methylphenidate |  | Predose, ½, 1, 1½, 2, 2½, 3, 4, 6, 8, 10, 24 and 33 hours post-dose | 
| Area under the plasma concentration versus time curve (AUC) of methylphenidate |  | Predose, ½, 1, 1½, 2, 2½, 3, 4, 6, 8, 10, 24 and 33 hours post-dose | 
| Peak plasma concentration (Cmax) of enalapril |  | Predose, ½, 1, 2, 3, 4, 5, 6, 9, 24, 48 and 72 hours post-dose | 
| Time to peak plasma concentration (Tmax) of enalapril |  | Predose, ½, 1, 2, 3, 4, 5, 6, 9, 24, 48 and 72 hours post-dose | 
| Terminal half life (t½) of enalapril |  | Predose, ½, 1, 2, 3, 4, 5, 6, 9, 24, 48 and 72 hours post-dose | 
| Area under the plasma concentration versus time curve (AUC) of enalapril |  | Predose, ½, 1, 2, 3, 4, 5, 6, 9, 24, 48 and 72 hours post-dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Metabolomic profile | Four samples for each participant during the methylphenidate trials (as indicated above). Metabolomics will be assessed with focus on lipids (lipid platform) and with use of usual concentration measures (eg nanomolar (nM)) | Predose/pre-meal, predose/post-meal, 2 and 6 hours post-dose |