Effect of Itraconazole and Ticlopidine on the Pharmacokinetics and Pharmacodynamics of Oral Tramadol

Pharmacokinetics Clinical Trial

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01214941
• Other study ID #: 54/180/2010
• Secondary ID: 2010-020617-82
• Status: Completed
• Phase: Phase 4
• First received: October 4, 2010
• Last updated: April 12, 2011
• Start date: September 2010
• Est. completion date: December 2010

Study information

• Verified date: October 2010
• Source: Turku University Hospital
• Contact: n/a
• Is FDA regulated: No
• Health authority: Finland: Finnish Medicines Agency
• Study type: Interventional

Clinical Trial Summary

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. The formation of inactive metabolites is catalysed by CYP3A4 and 2B6. This study is aimed to investigate the possible interaction of oral tramadol with itraconazole and ticlopidine, which are inhibitors of CYP3A4 and 2B6. 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 12
• Est. completion date: December 2010
• Est. primary completion date: December 2010
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 40 Years

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Pharmacokinetics/Dynamics Study, Intervention Model: Crossover Assignment, Masking: Single Blind (Subject), Primary Purpose: Basic Science

Related Conditions & MeSH terms

• Pharmacodynamics
• Pharmacokinetics

Intervention

Drug:
• Placebo
The subjects will be given orally placebo twice a day for 5 days prior to the study.
• Ticlopidine
The subjects will be given orally ticlopidine 250mg twice a day for 5 days prior to the study.
• Ticlopidine and itraconazole
The subjects will be given orally ticlopidine 250mg twice a day and itraconazole 200mg as a single daily dose for 5 days prior to the study.

Locations

Country	Name	City	State
Finland	Department of Anaesthesiology, Intensive Care, Emergency Care and Pain Medicine, Turku University and Turku University Hospital	Turku

Sponsors (1)

Lead Sponsor	Collaborator
Turku University Hospital

Country where clinical trial is conducted

Finland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	Metabolites of tramadol in urine	Urine will be collected for 24 hours and M1 and M2 metabolites of tramadol are quantified from 0-12h and 12-24h fractions	0-12 and 12-24 hour fractions after administration of tramadol	No
Secondary	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	No
Secondary	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	No
Secondary	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	No