Effects of LRYGB on Pharmacokinetics of Nine CYP Probe Drugs

Not Applicable

Completed

• Conditions: Obesity, Morbid; Bariatric Surgery Candidate
• Interventions: Drug: cocktail of nine CYP probe drugs

• Registration Number: NCT03563287
• Lead Sponsor: University of Eastern Finland

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2012-01-27
• Primary Completion: 2014-12-10
• Study Completion: 2014-12-10
• Status Verified: 2018-06
• Study First Submitted: 2018-06-08
• Study First Submitted QC: 2018-06-08
• Last Update Submitted: 2018-06-19
• Study First Posted: 2018-06-20
• Last Update Posted: 2018-06-21

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 13

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Phenotyping cocktail of 9 CYP probe drugs before surgery	cocktail of nine CYP probe drugs	-
Phenotyping cocktail of 9 CYP probe drugs 1 year after surgery	cocktail of nine CYP probe drugs	-

Primary Outcome Measures

Name	Time	Method
Probe cocktail drugs concentration-time profile in plasma and urine before LRYGB	baseline, 1 hour, 2 hour, 4 hour and 6 hour
Probe cocktail drugs concentration-time profile in plasma and urine 1 year after LRYGB	baseline, 1 hour, 2 hour, 4 hour and 6 hour

Secondary Outcome Measures

Name	Time	Method
Metabolic ratios of parent compounds and corresponding metabolites before LRYGB	baseline, 1 hour, 2 hour, 4 hour and 6 hour
Metabolic ratios of parent compounds and corresponding metabolites 1 year after LRYGB	baseline, 1 hour, 2 hour, 4 hour and 6 hour

Trial Locations

Locations (1)

University of Eastern Finland; 🇫🇮 Kuopio, Finland