Effects of LRYGB on Pharmacokinetics of Nine CYP Probe Drugs

Bariatric Surgery Candidate Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03563287
• Other study ID #: NUDROBE
• Status: Completed
• Phase: N/A
• Start date: January 27, 2012
• Est. completion date: December 10, 2014

Study information

• Verified date: June 2018
• Source: University of Eastern Finland
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 13
• Est. completion date: December 10, 2014
• Est. primary completion date: December 10, 2014
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 60 Years

Eligibility

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

Related Conditions & MeSH terms

• Bariatric Surgery Candidate
• Obesity
• Obesity, Morbid

Intervention

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.

Locations

Country	Name	City	State
Finland	University of Eastern Finland	Kuopio

Sponsors (5)

Lead Sponsor	Collaborator
University of Eastern Finland	Academy of Finland, Diabetes Research Foundation, Finland, Finnish Cultural Foundation, Kuopio University Hospital

Country where clinical trial is conducted

Finland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Probe cocktail drugs concentration-time profile in plasma and urine before LRYGB		baseline, 1 hour, 2 hour, 4 hour and 6 hour
Primary	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	Metabolic ratios of parent compounds and corresponding metabolites before LRYGB		baseline, 1 hour, 2 hour, 4 hour and 6 hour
Secondary	Metabolic ratios of parent compounds and corresponding metabolites 1 year after LRYGB		baseline, 1 hour, 2 hour, 4 hour and 6 hour