Kinetics of Fluvoxamine and Digoxin in Subjects With Different MDR1 Genotypes

The investigators will compare plasma kinetics of two marker drugs in individuals with different genetic variations in the MDR1-gene. The hypothesis is that one group will have higher exposure than the other.

Study Overview

• Status: Completed
• Conditions: Depression
• Intervention / Treatment: Drug: Digoxin; Drug: fluvoxamine

• Study Type: Interventional
• Enrollment (Actual): 14
• Phase: Phase 1

Contacts and Locations

Study Locations

• Sweden
  • Stockholm, Sweden
    • CPTU

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• - Healthy volunteer ≥ 18 years of age
• Normal kidney function as measured by GFR according to Cockroft-Gault (70-120 ml/min)
• Normal P-potassiumvalue (3,6-4,6 mmol/L)
• HF>50 and no AV-block on resting ECG. No other significant abnormalities as judged by the investigator.
• Subject giving written informed consent
• Subject capable of understanding instructions

Exclusion Criteria:

• - Pregnancy
• Ongoing infection
• Intake of medication, including natural remedies (for example St John´s wort), within one month prior to starting study except for paracetamol.
• Active drug or alcohol abuse

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 2677TT; Plasma kinetics of fluvoxamine and digoxin in this genotype	Drug: Digoxin; Drug: fluvoxamine
Other: 2677GG; plasma kinetics of fluvoxamine and digoxin in this genotype	Drug: Digoxin; Drug: fluvoxamine

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cmax of fluvoxamine and of digoxin	The participants are administered a single dose of fluvoxamine or digoxin. Plasma kinetics of fluvoxamine are followed for 36 hours. Plasma kinetics of digoxin are followed for 48 hours. There is a washout period between the both parts.	2 days for fluvoxamine and 2 days for digoxin. Washout period of at least 1 week between the both parts. Total study time maximum 4 weeks.

Collaborators and Investigators

• Sponsor: Karolinska Institutet

Study record dates

Study Major Dates

• Study Start: August 1, 2008
• Primary Completion (Actual): October 1, 2012
• Study Completion (Actual): October 1, 2012

Study Registration Dates

• First Submitted: September 21, 2012
• First Submitted That Met QC Criteria: October 10, 2012
• First Posted (Estimate): October 11, 2012

Study Record Updates

• Last Update Posted (Estimate): September 1, 2015
• Last Update Submitted That Met QC Criteria: August 31, 2015
• Last Verified: August 1, 2015

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Behavioral Symptoms; Depression; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Anti-Arrhythmia Agents; Central Nervous System Depressants; Enzyme Inhibitors; Protective Agents; Cardiotonic Agents; Tranquilizing Agents; Psychotropic Drugs; Serotonin Uptake Inhibitors; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Serotonin Agents; Antidepressive Agents; Anti-Anxiety Agents; Cytochrome P-450 Enzyme Inhibitors; Antidepressive Agents, Second-Generation; Cytochrome P-450 CYP1A2 Inhibitors; Cytochrome P-450 CYP2C19 Inhibitors; Digoxin; Fluvoxamine
• Other Study ID Numbers: fluvoxaminedigoxin