Bioavailability of Paracetamol, Amoxicillin and Talinolol Before, Immediately and One Year After Gastric Bypass Operation

NCT02514941 | Completed Phase 1

• 1 other identifier: Gastric Bypass
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 2

Brief Summary

The purpose of this study is to evaluate pharmacokinetics of paracetamol, amoxicillin and talinolol in morbid adipose subjects before as well as shortly after and about one year after proximal Roux-en-Y Gastric Bypass (RYGB) and to measure messenger ribonucleic acid (mRNA) expression and protein content of duodenal and/or jejunal drug metabolizing enzymes (eg. cytochrome P450 isoenzyme 3A4 (CYP3A4), uridine diphosphoglucuronosyltransferase (UGTs)) and drug transport proteins (e.g. P-glycoprotein, MRP2, OATPB, PEPT) before and during the operation and about one year after proximal RYGB.

Conditions

Morbid Obesity

Outcome Measures

Primary Outcomes (1)

• area under the concentration time curve of paracetamol, amoxicillin and talinolol

  up to 1.5 h before and 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, 24 h after study medication

Secondary Outcomes (5)

• maximal concentration of the concentration time curve of paracetamol, amoxicillin and talinolol

  up to 1.5 h before and 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, 24 h after study medication

• timepoint of the maximal concentration of the concentration time curve of paracetamol, amoxicillin and talinolol

  up to 1.5 h before and 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, 24 h after study medication

• terminal half-life of the concentration time curve of paracetamol, amoxicillin and talinolol

  up to 1.5 h before and 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, 24 h after study medication

• mRNA expression determined by quantitative polymerase chain reaction given as cycle threshold normalized to house keeping gene 18S and villin

  up to 2 days before the first study medication and after at least 6 h fasting, during proximal Roux-en-Y gastric bypass surgery within 3 days after first study medication and about one year after proximal Roux-en-Y gastric bypass surgery

• protein abundance determined by liquid chromatography-mass spectrometry based targeting proteomics normalized to villin

  up to 2 days before the first study medication and after at least 6 h fasting, during proximal Roux-en-Y gastric bypass surgery within 3 days after first study medication and about one year after proximal Roux-en-Y gastric bypass surgery

Study Arms (3)

pre OP

EXPERIMENTAL

The subjects will be administered 200 mg paracetamol, 250 mg amoxicillin and 50 mg talinolol dissolved in 40 ml water which must be drunken with additional 200 ml water on the first study day. This pharmacokinetic period will be performed within three days before the scheduled proximal Roux-en-Y gastric bypass surgery. A gastroduodenoscopy with biopsy of the lower duodenum will be performed before the first pharmacokinetic study period.

Drug: paracetamol; Drug: amoxicillin; Drug: talinolol; Procedure: gastroduodenoscopy with biopsy

post OP

EXPERIMENTAL

The subjects will be administered 200 mg paracetamol, 250 mg amoxicillin and 50 mg talinolol dissolved in 40 ml water which must be drunken with additional 200 ml water on the first study day. This pharmacokinetic period will be performed 5-7 days after the scheduled proximal Roux-en-Y gastric bypass surgery. A sampling of a tissue specimen from the jejunum will be collected during the operation.

Drug: paracetamol; Drug: amoxicillin; Drug: talinolol; Procedure: proximal Roux-en-Y gastric bypass

one year post OP

EXPERIMENTAL

The subjects will be administered 200 mg paracetamol, 250 mg amoxicillin and 50 mg talinolol dissolved in 40 ml water which must be drunken with additional 200 ml water on the first study day. This pharmacokinetic period and a gastrojejunoscopy with biopsy of the jejunum will be performed about one year after the scheduled proximal stomach bypass surgery.

Drug: paracetamol; Drug: amoxicillin; Drug: talinolol; Procedure: gastrojejunoscopy with biopsy

Interventions

paracetamol DRUG

Administration of 5 ml Paracetamol Saft Hexal (= 200 mg paracetamol)

Also known as: Paracetamol Saft Hexal

one year post OP; post OP; pre OP

amoxicillin DRUG

Administration of 5 ml Amoxypen® 250 mg Saft (= 250 mg amoxicillin)

Also known as: Amoxypen® 250 mg Saft

one year post OP; post OP; pre OP

talinolol DRUG

Administration of 1 tablet Cordanum® 50 (= 50 mg talinolol) dissolved with 40 ml tap water

Also known as: Cordanum® 50

one year post OP; post OP; pre OP

gastroduodenoscopy with biopsy PROCEDURE

Gastroduodenoscopy with biopsy of the lower duodenum before the first pharmacokinetic study period

pre OP

gastrojejunoscopy with biopsy PROCEDURE

Gastrojejunoscopy with biopsy of the jejunum about one year after proximal Roux-en-Y gastric bypass

one year post OP

proximal Roux-en-Y gastric bypass PROCEDURE

sampling of a tissue specimen from the jejunum during the operation

post OP

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• patients who are subjected to proximal stomach-bypass surgery by entire medical reasons independent of the objectives of this study
• age: over 18 years
• sex: male and female
• ethnic origin: Caucasian
• written informed consent

You may not qualify if:

• abnormal low hemoglobin values (\< 6.5 mmol/l \[female\]; \< 7.6 mmol/l \[male\])
• obstructive lung disease (e.g. bronchial asthma)
• acute myocardial infarction
• peripheral arterial circulatory disturbance
• any disturbance of impulse formation and conduction
• bradycardia (\< 50 beats/min)
• hypotension (systolic pressure \< 90 mmHg)
• phaeochromocytoma
• subjects who are unable to understand the written and verbal instructions, in particular regarding the risks and inconveniences they will be exposed to as a result of their participation in the study
• blood donation or other blood loss of more than 400 ml within the last 3 months prior to the start of the study
• participation in a clinical trial during the last 3 months prior to the start of the study
• less than 14 days after last acute disease
• treatment with paracetamol, amoxicillin or talinolol 7 days before the study
• repeated use of drugs during the last 4 weeks prior to the intended first administration, which can influence drug biotransformation and drug transport
• intake of grapefruit containing food or beverages within 7 days prior to administration

Sponsors & Collaborators

• University Medicine Greifswald: lead

Study Sites (2)

Department of Clinical Pharmacology, Ernst-Moritz-Arndt-University Greifswald

Greifswald, Mecklenburg-Vorpommern, 17487, Germany

Location

Surgical Clinic of the Clinical Centre Suedstadt Rostock

Rostock, 18059, Germany

Location

MeSH Terms

Conditions

Obesity, Morbid

Interventions

Acetaminophen; Amoxicillin; talinolol; Biopsy

Condition Hierarchy (Ancestors)

Obesity; Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Acetanilides; Anilides; Amides; Organic Chemicals; Aniline Compounds; Amines; Ampicillin; Penicillin G; Penicillins; beta-Lactams; Lactams; Sulfur Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Cytodiagnosis; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Specimen Handling; Diagnostic Techniques, Surgical; Surgical Procedures, Operative; Investigative Techniques

Study Officials

• Werner Siegmund, Prof

  Department of Clinical Pharmacology

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 29, 2015
• First Posted: August 4, 2015
• Study Start: June 1, 2007
• Primary Completion: March 1, 2010
• Last Updated: August 4, 2015

Record last verified: 2015-07

Locations

DE (2)