Influence of Diabetes on Tramadol Pharmacokinetics

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

COMPLETED

Clinical Phase

PHASE4

Total Enrollment

30 participants

Study Classification

INTERVENTIONAL

Study Start Date

2008-06-30

Study Completion Date

2011-12-31

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

This study aimed to investigate the influence of uncontrolled type 1 and type 2 diabetes mellitus (DM) on the kinetic disposition, metabolism and pharmacokinetics-pharmacodynamics of tramadol enantiomers in patients with neuropathic pain. Thus, nondiabetic patients (control group, n = 12), patients with type 1 DM (n = 9), and patients with type 2 DM (n = 9), all with neuropathic pain and phenotyped as extensive metabolizers of cytochrome P450 2D6 (CYP2D6) who were treated with a single oral dose of 100 mg racemic tramadol were investigated.

Related Clinical Trials

Explore similar clinical trials based on study characteristics and research focus.

A Pharmacodynamic/Pharmacokinetic Study to Determine the Onset of Analgesic Effect and Plasma Levels of Tramadol in Patients With Acute Low Back Pain Receiving a Single 200 mg Dose of Tramadol Contramid® Once-a-Day

NCT00952068

Acute Low Back Pain

COMPLETED PHASE2

Efficacy, Safety, Tolerability and Pharmacokinetics of Concomitant Administration of Tramadol With Duloxetine or Pregabalin

NCT01116531

Diabetic Polyneuropathy Postherpetic Neuralgia

WITHDRAWN PHASE4

PK PD of the Enantiomers of Tramadol and O-desmethyltramadol in Elderly and Young Subjects

NCT02329561

Aging Pain

COMPLETED PHASE1

Omnitram Pharmacokinetic Study In Healthy Volunteers

NCT02205554

Pain

COMPLETED PHASE1

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

NCT01214941

Pharmacokinetics Pharmacodynamics

COMPLETED PHASE4

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

Tramadol is a centrally acting analgesic that effectively relieves acute and chronic pain, including neuropathic pain in diabetic patients. The drug is available in clinical practice as a mixture of the (+)-tramadol and (-)-tramadol enantiomers. Tramadol is metabolized by CYP2D6 to O-desmethyltramadol (M1) and by cytochrome P450 3A (CYP3A4) and cytochrome P450 2B6 (CYP2B6) to N-desmethyltramadol (M2). Both tramadol enantiomers and (+)-M1 contribute to the analgesic activity of the drug: (+)-tramadol and the (+)-M1 metabolite act as -opioid receptor agonists; (+)-tramadol inhibits serotonin reuptake; and (-)-tramadol inhibits the reuptake of norepinephrine. This study investigated the influence of uncontrolled type 1 and type 2 diabetes mellitus (DM) on the kinetic disposition, metabolism and pharmacokinetics-pharmacodynamics of tramadol enantiomers in patients with neuropathic pain. Nondiabetic patients (control group, n = 12), patients with type 1 DM (n = 9), and patients with type 2 DM (n = 9), all with neuropathic pain and phenotyped as extensive metabolizers of CYP2D6, received a single oral dose of 100 mg racemic tramadol. Serial blood samples were collected up to 24 h after administration of the drug for pharmacokinetic study and for the analysis of noradrenaline in plasma. Pain was rated on a visual analog pain scale at the same time as blood sampling. The patients were evaluated for in vivo CYP3A activity using midazolam as a probe drug and genotyped for CYP2B6. Total and unbound plasma concentrations of the tramadol, M1 and M2 enantiomers were analyzed by liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS).

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Neuropathic Pain Type 1 Diabetes Mellitus Type 2 Diabetes Mellitus

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

Control group

Patients received a single oral dose of 100 mg racemic tramadol. Serial blood samples were collected up to 24 h after administration of the drug for pharmacokinetic study and for the analysis of noradrenaline in plasma. Pain was rated on a visual analog pain scale at the same time as blood sampling. CYP2D6 phenotype was evaluated using metoprolol as probe drug. CYP3A phenotype was evaluated using midazolam. Patients were genotyped for the single nucleotide polymorphism (SNP) 516G\>T in CYP2B6 gene (CYP2B6 genotype).

Group Type ACTIVE_COMPARATOR

Single oral dose of 100 mg racemic tramadol

Intervention Type DRUG

Serial blood samples were collected up to 24 h after drug administration; Pain was evaluated at the same time of blood sampling using visual analog scale

CYP2D6 phenotype

Intervention Type OTHER

Patients were phenotyped using metoprolol (100 mg, single oral dose). Urine was collected up to 8 hours after metoprolol administration. Urinary concentrations of metoprolol and alfa-hydroxymetoprolol were determined by high performance liquid chromatography (HPLC), using fluorescence detector.

CYP2D6 phenotyped was determined by alfa-hydroxymetoprolol/metoprolol urinary rato

CYP3A phenotype

Intervention Type OTHER

A single oral dose of midazolam (15 mg) was administered to all patients. Serial blood samples were collected up to 6 hours after the administration of midazolam.

The concentration of midazolam was determined in plasma in order to calculate midazolam clearance.

The in vivo activity of CYP3A was evaluated by midazolam oral clearance.

CYP2B6 genotype

Intervention Type GENETIC

The single nucleotide polymorphism 516G\>T in CYP2B6 gene was evaluated using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP).

T2DM group

Patients received a single oral dose of 100 mg racemic tramadol. Serial blood samples were collected up to 24 h after administration of the drug for pharmacokinetic study and for the analysis of noradrenaline in plasma. Pain was rated on a visual analog pain scale at the same time as blood sampling. CYP2D6 phenotype was evaluated using metoprolol as probe drug. CYP3A phenotype was evaluated using midazolam. Patients were genotyped for SNP 516G\>T in CYP2B6 gene (CYP2B6 genotype).

The diagnosis of type 2 DM was performed according to the American Diabetes Association (2010).

Group Type EXPERIMENTAL

Single oral dose of 100 mg racemic tramadol

Intervention Type DRUG

Serial blood samples were collected up to 24 h after drug administration; Pain was evaluated at the same time of blood sampling using visual analog scale

CYP2D6 phenotype

Intervention Type OTHER

Patients were phenotyped using metoprolol (100 mg, single oral dose). Urine was collected up to 8 hours after metoprolol administration. Urinary concentrations of metoprolol and alfa-hydroxymetoprolol were determined by high performance liquid chromatography (HPLC), using fluorescence detector.

CYP2D6 phenotyped was determined by alfa-hydroxymetoprolol/metoprolol urinary rato

CYP3A phenotype

Intervention Type OTHER

A single oral dose of midazolam (15 mg) was administered to all patients. Serial blood samples were collected up to 6 hours after the administration of midazolam.

The concentration of midazolam was determined in plasma in order to calculate midazolam clearance.

The in vivo activity of CYP3A was evaluated by midazolam oral clearance.

CYP2B6 genotype

Intervention Type GENETIC

The single nucleotide polymorphism 516G\>T in CYP2B6 gene was evaluated using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP).

T1DM group

Patients received a single oral dose of 100 mg racemic tramadol. Serial blood samples were collected up to 24 h after administration of the drug for pharmacokinetic study and for the analysis of noradrenaline in plasma. Pain was rated on a visual analog pain scale at the same time as blood sampling. CYP2D6 phenotype was evaluated using metoprolol as probe drug. CYP3A phenotype was evaluated using midazolam. Patients were genotyped for SNP 516G\>T in CYP2B6 gene (CYP2B6 genotype).

The diagnosis of type 1 DM was performed according to the American Diabetes Association (2010).

Group Type EXPERIMENTAL

Single oral dose of 100 mg racemic tramadol

Intervention Type DRUG

Serial blood samples were collected up to 24 h after drug administration; Pain was evaluated at the same time of blood sampling using visual analog scale

CYP2D6 phenotype

Intervention Type OTHER

Patients were phenotyped using metoprolol (100 mg, single oral dose). Urine was collected up to 8 hours after metoprolol administration. Urinary concentrations of metoprolol and alfa-hydroxymetoprolol were determined by high performance liquid chromatography (HPLC), using fluorescence detector.

CYP2D6 phenotyped was determined by alfa-hydroxymetoprolol/metoprolol urinary rato

CYP3A phenotype

Intervention Type OTHER

A single oral dose of midazolam (15 mg) was administered to all patients. Serial blood samples were collected up to 6 hours after the administration of midazolam.

The concentration of midazolam was determined in plasma in order to calculate midazolam clearance.

The in vivo activity of CYP3A was evaluated by midazolam oral clearance.

CYP2B6 genotype

Intervention Type GENETIC

The single nucleotide polymorphism 516G\>T in CYP2B6 gene was evaluated using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP).

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

Single oral dose of 100 mg racemic tramadol

Serial blood samples were collected up to 24 h after drug administration; Pain was evaluated at the same time of blood sampling using visual analog scale

Intervention Type DRUG

CYP2D6 phenotype

Patients were phenotyped using metoprolol (100 mg, single oral dose). Urine was collected up to 8 hours after metoprolol administration. Urinary concentrations of metoprolol and alfa-hydroxymetoprolol were determined by high performance liquid chromatography (HPLC), using fluorescence detector.

CYP2D6 phenotyped was determined by alfa-hydroxymetoprolol/metoprolol urinary rato

Intervention Type OTHER

CYP3A phenotype

A single oral dose of midazolam (15 mg) was administered to all patients. Serial blood samples were collected up to 6 hours after the administration of midazolam.

The concentration of midazolam was determined in plasma in order to calculate midazolam clearance.

The in vivo activity of CYP3A was evaluated by midazolam oral clearance.

Intervention Type OTHER

CYP2B6 genotype

The single nucleotide polymorphism 516G\>T in CYP2B6 gene was evaluated using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP).

Intervention Type GENETIC

Other Intervention Names

Discover alternative or legacy names that may be used to describe the listed interventions across different sources.

Tramadol treament Blood sampling Tramadol pharmacokinetics CYP2D6 phenotyping CYP2D6 in vivo activity CYP3A phenotyping CYP3A in vivo activity Genotype of SNP 516G>T in CYP2B6

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

Inclusion Criteria

* Adult patients, both gender
* Patients with self-reported neuropathic pain (score \>4 in a 0-10 visual analog scale)
* Patients with normal renal function (creatinine clearance \>60 mL/min)

Exclusion Criteria

* Patients with nociceptive somatic pain, visceral or autonomic associated during the study period;
* Patients with morbid obesity (BMI\> 40), congestive heart failure, severe hypertension
* Patients who have had acute myocardial infarction or accident stroke less than 6 months of the period of investigation.
* Patients with chronic obstructive pulmonary disease
* Patients who were in use of analgesics, CYP2D6 inhibitors or CYP3A4 inducers or inhibitors were excluded.
* Pregnant and lactating patients were excluded.

Minimum Eligible Age

18 Years

Maximum Eligible Age

59 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No