Impact of Polymorphisms of OCT2 and OCTN1 on the Kinetic Disposition of Gabapentin in Patients Undergoing Chronic Use

Impact of Polymorphisms of OCT2 and OCTN1 on the Kinetic Disposition of Gabapentin in Patients Undergoing Chronic Use

Impact of Genetic Polymorphisms of OCT2 and OCTN1 on the Kinetic Disposition of Gabapentin in Patients Undergoing Chronic Use of the Drug

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.

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).

Patients with 18 years old or older with epilepsy, neuropathic pain or any chronic pain undergoing chronic treatment with gabapentin are being recruited. Sparse blood sampling are being collected up to 4 h after administration of the drug for pharmacokinetic study. Urine sampling are being collected during the dosing interval, only in patients hospitalized at the Hospital Estadual de Américo Brasiliense (HEAB). Blood sample are being collected for DNA extraction. DNA are being extracted from the whole blood of all patients for genotyping of the SLC22A2 c.808G>T and SLC22A4 c.1507C>T polymorphisms.

Patients with 18 years old or older with epilepsy, neuropathic pain or any chronic pain undergoing chronic treatment with gabapentin are being recruited. Sparse blood sampling are being collected up to 4 h after administration of the drug for pharmacokinetic study. Urine sampling are being collected during the dosing interval, only in patients hospitalized at the Hospital Estadual de Américo Brasiliense (HEAB). Blood sample are being collected for DNA extraction. DNA are being extracted from the whole blood of all patients for genotyping of the SLC22A2 c.808G>T and SLC22A4 c.1507C>T polymorphisms.

Urine samples are being collected during the dosing interval, only in patients hospitalized at Hospital Estadual de Américo Brasiliense (HEAB).

Blood sample are being collected for DNA extraction. DNA are being extracted from the whole blood of all patients for genotyping of the SLC22A2 c.808G>T and SLC22A4 c.1507C>T polymorphisms

Blood samples will be collected at 0, 90 and 240 minutes after gabapentin administration. The gabapentin plasma concentration will be assessed using liquid chromatography with UV detection (LC-UV).

The single nucleotide polymorphisms of SLC22A2 gene (c.808G>T) and SLC22A4 (c.1507C>T) are being evaluated in all included patients.

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.