Effects of LRYGB on Pharmacokinetics of Nine CYP Probe Drugs

NCT ID: NCT03563287

Last Updated: 2018-06-21

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 13 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-01-27
• Study Completion Date: 2014-12-10

Brief Summary

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.

Conditions

Obesity, Morbid; Bariatric Surgery Candidate

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: DIAGNOSTIC
• Blinding Strategy: NONE

Study Groups

Phenotyping cocktail of 9 CYP probe drugs before surgery

Group Type: EXPERIMENTAL

cocktail of nine CYP probe drugs

Intervention Type: DRUG

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.

Phenotyping cocktail of 9 CYP probe drugs 1 year after surgery

Group Type: EXPERIMENTAL

cocktail of nine CYP probe drugs

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: DRUG

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 60 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Diabetes Research Foundation, Finland

OTHER

Sponsor Role: collaborator

Finnish Cultural Foundation

OTHER

Sponsor Role: collaborator

Kuopio University Hospital

OTHER

Sponsor Role: collaborator

Academy of Finland

OTHER

Sponsor Role: collaborator

University of Eastern Finland

OTHER

Sponsor Role: lead

Responsible Party

Jussi Pihlajamäki

Prof.

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

University of Eastern Finland

Kuopio, , Finland

Countries

Finland

Other Identifiers

NUDROBE

Identifier Type: -

Identifier Source: org_study_id