Effect of Celecoxib and Etoricoxib on the Pharmacokinetics and Pharmacodynamics of Oral Tramadol

Tramadol is an opioid analgesic, which is widely used in the treatment of acute and neuropathic pain. After oral administration, tramadol is rapidly and almost completely absorbed. Tramadol is extensively metabolised by O- and N-demethylation, which are catalysed by the liver CYP-450 enzymes. O-desmethyltramadol is an active metabolite and its formation is catalysed by CYP2D6. This study is aimed to investigate the possible interaction of oral tramadol with selecoxib and etoricoxib. Selecoxib is known to inhibit CYP2D6. Twelve healthy male or female adult non-smoking volunteers aged 18-40 years with body weights within ±15% of the ideal weight for height are taken into the study. Primary endpoints of the study are plasma concentrations of tramadol and its metabolites.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: Placebo; Drug: Selecoxib; Drug: Etoricoxib

• Study Type: Interventional
• Enrollment (Anticipated): 12
• Phase: Phase 1

Contacts and Locations

Study Locations

• Finland
  • Turku, Finland
    • Department of Anaesthesiology, Intensive Care, Emergency Care and Pain Medicine, Turku University and Turku University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 38 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Healthy volunteers
• Age 18-40
• Body weight within ±15% of the ideal weight for height

Exclusion Criteria:

• A previous history of intolerance to the study drugs or to related compounds and additives
• Concomitant drug therapy of any kind for at least 14 days prior to the study
• Existing or recent significant disease
• History of hematological, endocrine, metabolic or gastrointestinal disease, including gut motility disorders
• History of asthma or any kind of drug allergy
• Previous or present alcoholism, drug abuse, psychological or other emotional problems that are likely to invalidate informed consent, or limit the ability of the subject to comply with the protocol requirements
• A positive test result for urine toxicology
• A "yes" answer to any one of the Abuse Questions
• Pregnancy or nursing
• Donation of blood for 4 weeks prior and during the study
• Special diet or life style conditions which would compromise the conditions of the study or interpretation of the results
• Participation in any other studies involving investigational or marketed drug products concomitantly or within one month prior to the entry into this study
• Smoking for one month before the start of the study and during the whole study period
• Any history of coagulation abnormality, also in first degree relatives

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Single

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo; The subjects will be given orally placebo twice a day for 7 days prior to the study.
Active Comparator: Selecoxib	Drug: Selecoxib; The subjects will be given orally selecoxib 200mg twice a day for 7 days prior to the study.
Active Comparator: Etoricoxib	Drug: Etoricoxib; The subjects will be given orally etoricoxib 120mg once a day for 7 days prior to the study.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Concentration of tramadol and its metabolites in plasma	0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 24, 48 hours after administration of tramadol

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Serotonin concentrations	Serotonin concentrations will be analyzed with chromatographical methods from the blood samples drawn 0, 4 and 8 hours after tramadol administration	0, 4 and 8 hours after tramadol administration
Pharmacodynamic effects	The psychomotor effects of tramadol will be assessed with the measurement of pupil size with Cogan's pupillometer, Maddox wing test and digit symbol substitution test	1, 2, 3, 4, 5, 6, 8, 10, 12 hours after administration of tramadol
Analgesia	The analgesic effect of tramadol will be evaluated using the cold pressor test. Briefly, the subject's hand is immersed into ice-cold water of + 4° C up to the wrist. The subject is told to keep his or her hand in the water and to report when the cold sensation becomes painful. Cold pain threshold is defined as the latency from the immersion of the hand to the subject's first report of pain. Cold pain intensity is assessed at 30 s intervals following immersion of the hand in cold water for up to 60s . A verbal numerical rating scale of 0-100 will be used.	1, 2, 3, 4, 5, 6, 8, 10, 12 hours after the administration of tramadol

Collaborators and Investigators

• Sponsor: Turku University Hospital

Study record dates

Study Major Dates

• Study Start: January 1, 2011
• Primary Completion (Actual): July 1, 2011
• Study Completion (Actual): July 1, 2011

Study Registration Dates

• First Submitted: February 24, 2011
• First Submitted That Met QC Criteria: February 24, 2011
• First Posted (Estimate): February 25, 2011

Study Record Updates

• Last Update Posted (Estimate): July 11, 2011
• Last Update Submitted That Met QC Criteria: July 8, 2011
• Last Verified: July 1, 2011

More Information

Terms related to this study

• Keywords: Pharmacokinetics; Pharmacodynamics
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Cyclooxygenase Inhibitors; Cyclooxygenase 2 Inhibitors; Etoricoxib
• Other Study ID Numbers: 119/180/2010; 2010-023373-19 (EudraCT Number)