Influence of Diabetes on Tramadol Pharmacokinetics
Information source: Universidade Estadual Paulista Júlio de Mesquita Filho
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Neuropathic Pain; Type 1 Diabetes Mellitus; Type 2 Diabetes Mellitus
Intervention: Single oral dose of 100 mg racemic tramadol (Drug); CYP2D6 phenotype (Other); CYP3A phenotype (Other); CYP2B6 genotype (Genetic)
Phase: Phase 4
Status: Completed
Sponsored by: Universidade Estadual Paulista Júlio de Mesquita Filho Official(s) and/or principal investigator(s): Natalia V de Moraes, PhD, Principal Investigator, Affiliation: Universidade Estadual Paulista Julio de Mesquita Filho
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.
Clinical Details
Official title: Influence of Uncontrolled Diabetes on the Kinetic Disposition, Metabolism and Pharmacokinetics-pharmacodynamics of Tramadol Enantiomers in Patients With Neuropathic Pain
Study design: Allocation: Non-Randomized, Endpoint Classification: Pharmacokinetics/Dynamics Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Primary outcome: Kinetic parameters (AUC, Cmax, Tmax, apparent total clearance, and apparent volume of distribution) of tramadol enantiomers were estimated.
Secondary outcome: Urinary concentration ratio (metoprolol/alfa-hydroxymetoprolol) as an in vivo measure of CYP2D6 activityClearance of midazolam as a measure of CYP3A in vivo activity Pain scores on the visual analog scale
Detailed 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).
Eligibility
Minimum age: 18 Years.
Maximum age: 59 Years.
Gender(s): Both.
Criteria:
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.
Locations and Contacts
Universidade Estadual Paulista Julio de Mesquita Filho, Araraquara, SP 14801902, Brazil
Additional Information
Starting date: June 2008
Last updated: September 18, 2014
|