Effects of LRYGB on Pharmacokinetics of Nine CYP Probe Drugs

June 19, 2018 updated by: Jussi Pihlajamäki, University of Eastern Finland

Altered Metabolism of Nutrients and Drugs in Obesity and After Obesity Surgery

Due to anatomical and physiological changes caused by the Roux-en-Y gastric bypass (RYGB) bariatric surgery, drug bioavailability after the surgery can be altered. Therefore, post-operative dose adjustment in these patients can be required.

The aim of the study was to investigate the effects of laparoscopic Roux-en-Y gastric bypass (LRYGB) surgery on drug pharmacokinetics and cytochrome P450 (CYP) mediated metabolism using a cocktail of nine CYP probe drugs.

The cocktail covers nine main CYP enzymes: melatonin (CYP1A2), nicotine (CYP2A6), bupropion (CYP2B6), repaglinide (CYP2C8), losartan (CYP2C9), omeprazole (CYP2C19/CYP3A4), dextromethorphan (CYP2D6), chlorzoxazone (CYP2E1), midazolam (CYP3A4).

The changes in pharmacokinetic parameters of the drugs as well as modulation of the activity of CYPs are evaluated before and one year after LRYGB. In the study, the patients administering drug cocktail before surgery and 1 year after LRYGB are served as their own controls.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

13

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Finland
      • Kuopio, Finland
        • University of Eastern Finland

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 60 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • BMI > 40 kg/m2 or BMI 35-40 kg/m2 and a comorbidity or its risk factor, such as type 2 diabetes, hypertension, sleep apnea, osteoarthritis of weight bearing joints or polycystic ovarian syndrome;
  • previous conservative treatment for obesity had been proven to be ineffective;
  • patients were assigned to undergo LRYGB surgery
  • patients are able to give a written inform consent.

Exclusion Criteria:

  • smokers
  • consuming alcohol more than 20 g per day were included in the study
  • taking drugs which alter CYPs activity
  • history of hypersensitivity to the drugs used in the cocktail

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Diagnostic
  • Allocation: Non-Randomized
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Phenotyping cocktail of 9 CYP probe drugs before surgery
Drug: cocktail of nine CYP probe drugs

Two equally loaded capsules containing:

Melatonin (2.0 mg) Nicotine (1.0 mg) Bupropion (37.5 mg) Repaglinide (0.25 mg) Losartan (12.5 mg) Omeprazole (10 mg) Chlorzoxazone (62.5 mg) Midazolam (1.85 mg) Dextromethorphan (30 mg) as an oral solution was administered separately after the capsules.
Experimental: Phenotyping cocktail of 9 CYP probe drugs 1 year after surgery
Drug: cocktail of nine CYP probe drugs

Two equally loaded capsules containing:

Melatonin (2.0 mg) Nicotine (1.0 mg) Bupropion (37.5 mg) Repaglinide (0.25 mg) Losartan (12.5 mg) Omeprazole (10 mg) Chlorzoxazone (62.5 mg) Midazolam (1.85 mg) Dextromethorphan (30 mg) as an oral solution was administered separately after the capsules.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Probe cocktail drugs concentration-time profile in plasma and urine before LRYGB
Time Frame: baseline, 1 hour, 2 hour, 4 hour and 6 hour
baseline, 1 hour, 2 hour, 4 hour and 6 hour
Probe cocktail drugs concentration-time profile in plasma and urine 1 year after LRYGB
Time Frame: baseline, 1 hour, 2 hour, 4 hour and 6 hour
baseline, 1 hour, 2 hour, 4 hour and 6 hour

Secondary Outcome Measures

Outcome Measure
Time Frame
Metabolic ratios of parent compounds and corresponding metabolites before LRYGB
Time Frame: baseline, 1 hour, 2 hour, 4 hour and 6 hour
baseline, 1 hour, 2 hour, 4 hour and 6 hour
Metabolic ratios of parent compounds and corresponding metabolites 1 year after LRYGB
Time Frame: baseline, 1 hour, 2 hour, 4 hour and 6 hour
baseline, 1 hour, 2 hour, 4 hour and 6 hour

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Eastern Finland

Collaborators

Kuopio University Hospital
Finnish Cultural Foundation
Academy of Finland
Diabetes Research Foundation, Finland

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 27, 2012

Primary Completion (Actual)

December 10, 2014

Study Completion (Actual)

December 10, 2014

Study Registration Dates

First Submitted

June 8, 2018

First Submitted That Met QC Criteria

June 8, 2018

First Posted (Actual)

June 20, 2018

Study Record Updates

Last Update Posted (Actual)

June 21, 2018

Last Update Submitted That Met QC Criteria

June 19, 2018

Last Verified

June 1, 2018

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • NUDROBE

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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