Influence of Diabetes on Tramadol Pharmacokinetics

Last updated: September 18, 2014
Sponsor: Universidade Estadual Paulista Júlio de Mesquita Filho
Overall Status: Completed

Phase

4

Condition

Diabetes Mellitus, Type 1

Neuropathy

Acute Pain

Treatment

N/A

Clinical Study ID

NCT02246712
DIABETRA
  • Ages 18-59
  • All Genders

Study Summary

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.

Eligibility Criteria

Inclusion

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

Exclusion Criteria:

  • Patients with nociceptive somatic pain, visceral or autonomic associated during thestudy period;

  • Patients with morbid obesity (BMI> 40), congestive heart failure, severe hypertension

  • Patients who have had acute myocardial infarction or accident stroke less than 6months of the period of investigation.

  • Patients with chronic obstructive pulmonary disease

  • Patients who were in use of analgesics, CYP2D6 inhibitors or CYP3A4 inducers orinhibitors were excluded.

  • Pregnant and lactating patients were excluded.

Study Design

Total Participants: 30
Study Start date:
June 01, 2008
Estimated Completion Date:
December 31, 2011

Study Description

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).

Connect with a study center

  • Universidade Estadual Paulista Julio de Mesquita Filho

    Araraquara, SP 14801902
    Brazil

    Site Not Available

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