Effects of LRYGB on Pharmacokinetics of Nine CYP Probe Drugs

University of Eastern Finland13 enrolled

Overview

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 Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

DIAGNOSTIC

Masking

NONE

Enrollment

Conditions

Obesity, Morbid Bariatric Surgery Candidate

Interventions

cocktail of nine CYP probe drugsDRUG

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.

Eligibility

Sex: ALLMin age: 18 YearsMax age: 60 Years

Medical Language ↔ Plain English

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

Outcomes

Primary Outcomes

Probe cocktail drugs concentration-time profile in plasma and urine before LRYGB

Time frame: 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

Secondary Outcomes

Metabolic ratios of parent compounds and corresponding metabolites before LRYGB

Time frame: 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

Effects of LRYGB on Pharmacokinetics of Nine CYP Probe Drugs

Overview

Conditions

Interventions

Eligibility

Locations (1)

Outcomes

Primary Outcomes

Secondary Outcomes