Clinical trial NCT01214941: Effect of Itraconazole and Ticlopidine on the Pharmacokinetics and Pharmacodynamics of Oral Tramadol
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Pharmacokinetics
Pharmacodynamics
Lead sponsor: Turku University Hospital
Sponsor class: OTHER_GOV
First posted: 2010-10-05
Enrollment: 12
Sex: ALL
Minimum age (years): 18
Maximum age (years): 40
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: BASIC_SCIENCE

Brief 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.


Eligibility criteria: 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

Primary outcomes:
measure: Concentration of tramadol and its metabolites in plasma
timeFrame: 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 24, 48 hours after administration of tramadol
Secondary outcomes:
measure: Metabolites of tramadol in urine
timeFrame: 0-12 and 12-24 hour fractions after administration of tramadol
measure: Serotonin concentrations
timeFrame: 0, 4 and 8 hours after tramadol administration
measure: Pharmacodynamic effects
timeFrame: 1, 2, 3, 4, 5, 6, 8, 10, 12 hours after administration of tramadol
measure: Analgesia
timeFrame: 1, 2, 3, 4, 5, 6, 8, 10, 12 hours after the administration of tramadol
Other outcomes:
Locations:
city: Turku
country: Finland
facility: Department of Anaesthesiology, Intensive Care, Emergency Care and Pain Medicine, Turku University and Turku University Hospital
Study officials:
affiliation: Turku University Hospital and Turku University
name: Klaus T Olkkola, MD, PhD, Prof
role: PRINCIPAL_INVESTIGATOR
References:
citation: Hagelberg NM, Saarikoski T, Saari TI, Neuvonen M, Neuvonen PJ, Turpeinen M, Scheinin M, Laine K, Olkkola KT. Ticlopidine inhibits both O-demethylation and renal clearance of tramadol, increasing the exposure to it, but itraconazole has no marked effect on the ticlopidine-tramadol interaction. Eur J Clin Pharmacol. 2013 Apr;69(4):867-75. doi: 10.1007/s00228-012-1433-0. Epub 2012 Oct 26.