Metabolism of Methylphenidate and Enalapril Based on CES1 Genotype

Overview

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 Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Non-Randomized
    • Intervention Model: Crossover Assignment
    • Primary Purpose: Basic Science
    • Masking: None (Open Label)
  • Study Primary Completion Date: May 2014

Interventions

  • Drug: Methylphenidate
    • 10 mg as a single dose followed by blood samples for the next 33 hours
  • Drug: Enalapril
    • 10 mg as a single dose followed by blood samples for the next 72 hours

Arms, Groups and Cohorts

  • Experimental: Methylphenidate
  • Experimental: Enalapril

Clinical Trial Outcome Measures

Primary Measures

  • Peak plasma concentration (Cmax) of methylphenidate
    • Time Frame: 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
    • Time Frame: Predose, ½, 1, 1½, 2, 2½, 3, 4, 6, 8, 10, 24 and 33 hours post-dose
  • Terminal half life (t½) of methylphenidate
    • Time Frame: 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
    • Time Frame: Predose, ½, 1, 1½, 2, 2½, 3, 4, 6, 8, 10, 24 and 33 hours post-dose
  • Peak plasma concentration (Cmax) of enalapril
    • Time Frame: Predose, ½, 1, 2, 3, 4, 5, 6, 9, 24, 48 and 72 hours post-dose
  • Time to peak plasma concentration (Tmax) of enalapril
    • Time Frame: Predose, ½, 1, 2, 3, 4, 5, 6, 9, 24, 48 and 72 hours post-dose
  • Terminal half life (t½) of enalapril
    • Time Frame: 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
    • Time Frame: Predose, ½, 1, 2, 3, 4, 5, 6, 9, 24, 48 and 72 hours post-dose

Secondary Measures

  • Metabolomic profile
    • Time Frame: Predose/pre-meal, predose/post-meal, 2 and 6 hours post-dose
    • 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))

Participating in This Clinical Trial

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)

Gender Eligibility: All

Minimum Age: 18 Years

Maximum Age: N/A

Are Healthy Volunteers Accepted: Accepts Healthy Volunteers

Investigator Details

  • Lead Sponsor
    • Bispebjerg Hospital
  • Collaborator
    • The Ministry of Science, Technology and Innovation, Denmark
  • Provider of Information About this Clinical Study
    • Principal Investigator: Gesche Jurgens, M.D., Ph.D. – Bispebjerg Hospital
  • Overall Official(s)
    • Gesche Jürgens, M.D., Principal Investigator, Department of Clinical Pharmacology, Bispebjerg University Hospital

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