Metabolism of Methylphenidate and Enalapril Based on CES1 Genotype

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.

Study Overview

• Status: Completed
• Conditions: Carboxylesterase 1 (CES1) Genotype; CES1 Activity
• Intervention / Treatment: Drug: Methylphenidate; Drug: Enalapril

• Study Type: Interventional
• Enrollment (Actual): 44
• Phase: Phase 4

Contacts and Locations

Study Locations

• Denmark
  • Copenhagen, Denmark, 2400
    • Department of Clinical Pharmacology, Bispebjerg University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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)

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Methylphenidate	Drug: Methylphenidate; 10 mg as a single dose followed by blood samples for the next 33 hours; Other Names: Ritalin
Experimental: Enalapril	Drug: Enalapril; 10 mg as a single dose followed by blood samples for the next 72 hours; Other Names: Corodil

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: Bispebjerg Hospital
• Collaborators: University of Copenhagen; Duke University; The Ministry of Science, Technology and Innovation, Denmark; Mental Health Centre Sct. Hans (Denmark); The Leiden Academic Center for Drug Research (LACDR)
• Investigators: Principal Investigator: Gesche Jürgens, M.D., Department of Clinical Pharmacology, Bispebjerg University Hospital

Study record dates

Study Major Dates

• Study Start: April 1, 2012
• Primary Completion (Actual): May 1, 2014
• Study Completion (Actual): May 1, 2014

Study Registration Dates

• First Submitted: July 1, 2013
• First Submitted That Met QC Criteria: May 8, 2014
• First Posted (Estimate): May 9, 2014

Study Record Updates

• Last Update Posted (Estimate): July 30, 2014
• Last Update Submitted That Met QC Criteria: July 29, 2014
• Last Verified: July 1, 2014

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Antihypertensive Agents; Enzyme Inhibitors; Protease Inhibitors; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Dopamine Agents; Dopamine Uptake Inhibitors; Central Nervous System Stimulants; Angiotensin-Converting Enzyme Inhibitors; Methylphenidate; Enalapril
• Other Study ID Numbers: INDICES-WP2