Effects of LRYGB on Pharmacokinetics of Nine CYP Probe Drugs

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

Status

Completed

Phases

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT03563287

Enrollment

Registered

2018-06-20

Start date

2012-01-27

Completion date

2014-12-10

Last updated

2018-06-21

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Bariatric Surgery Candidate, Obesity, Morbid

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.

Interventions

DRUGcocktail 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.

Study design

Allocation

NON_RANDOMIZED

Intervention model

SINGLE_GROUP

Primary purpose

DIAGNOSTIC

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to 60 Years

Healthy volunteers

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

Design outcomes

Primary

Measure	Time frame
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

Measure	Time frame
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

Countries

Finland

Outcome results

None listed

Source: ClinicalTrials.gov · Data processed: Feb 4, 2026