Clinical trial NCT02977208: Impact of Polymorphisms of OCT2 and OCTN1 on the Kinetic Disposition of Gabapentin in Patients Undergoing Chronic Use
Official title: Impact of Genetic Polymorphisms of OCT2 and OCTN1 on the Kinetic Disposition of Gabapentin in Patients Undergoing Chronic Use of the Drug
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Epilepsy
Chronic Pain
Keywords: Gabapentin
OCT2
OCTN1
Pharmacogenetics
Pharmacokinetics
Polymorphisms
Lead sponsor: São Paulo State University
Sponsor class: OTHER
Collaborators: name: University of Sao Paulo
First posted: 2016-11-30
Enrollment: 66
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study aims to evaluate the influence of genetic polymorphisms of OCTN1 and OCT2 and other possible covariates on the kinetic disposition of GAB in patients undergoing GAB chronic treatment. Thus, patients treated with GAB, for at least one week, are being investigated.

Detailed description: Gabapentin (GAB), an anticonvulsant used for the treatment of epilepsy and chronic pain, has nonlinear kinetics, it is not metabolized and it is mainly eliminated by renal excretion. Studies suggest that the renal excretion of GAB is dependent on active secretion by organic cation transporter 2 (OCT2) and organic cation/ergothioneine transporter 1 (OCTN1). These transporters are expressed at the membrane of the renal proximal tubules and they are involved in the elimination of endogenous compounds and many drugs. The genetic polymorphism of drug transporters has been studied to explain the kinetic disposition variability of their substrates. The objective of this study is to investigate the influence of genetic polymorphisms of OCTN1 and OCT2 and other possible covariates (e.g., sex, age, creatinine clearance, body mass index) on the kinetic disposition of GAB in patients undergoing GAB chronic treatment. Patients treated with GAB, for at least one week, are being investigated. Blood and urine samples are being collected to GAB pharmacokinetic analysis, serum creatinine analysis and for genotyping. The plasma concentration of GAB will be assessed using liquid chromatography with UV detection (LC-UV).

Eligibility criteria: Inclusion Criteria:

* Patients with 18 years old or older, both gender.
* Patients undergoing chronic use of gabapentin (at least one week).

Exclusion Criteria:

* Pregnant and lactating patients.
* Patients who were in use of OCT2 and OCTN1 inhibitors.
* Patients who disagree to continue the study.

Primary outcomes:
measure: Gabapentin plasma concentration.
timeFrame: Up to 240 minutes after gabapentin administration.
measure: OCT2 and OCTN1 genotyping
timeFrame: Up to 5 minutes before gabapentin administration
Secondary outcomes:
Other outcomes:
Locations:
city: Araraquara
country: Brazil
facility: Universidade Estadual Paulista Júlio de Mesquita Filho
state: São Paulo
Study officials:
affiliation: University of Sao Paulo
name: Fabíola D. Eckeli, Prof.
role: PRINCIPAL_INVESTIGATOR
affiliation: Hospital Estadual de Américo Brasiliense
name: Edgar Ianhez Júnior
role: PRINCIPAL_INVESTIGATOR
affiliation: Universidade Estadual Paulista Júlio de Mesquita Filho
name: Natália V. de Moraes, Prof.
role: STUDY_CHAIR
References: