NCT03047278

Transporters for Organic Cations and Glycemic Control in Patients With Neuropathic Pain.

Gabapentin Kinetic Disposition and Renal Excretion: Role of Transporters for Organic Cations and the Effect of Glycemic Control in Patients With Neuropathic Pain.

• Status: Completed
• Phase: Phase 4
• Study type: Interventional
• Enrollment: 29 (actual)
• Sponsor: Natalia Valadares de Moraes · Academic / Other
• Sex: All
• Age: 18 Years – 59 Years
• Healthy volunteers: Not accepted

Summary

This study aimed to investigate the influence of the glycemic control of type 2 diabetes (DM2) and of cetirizine (OCTs inhibitor) on gabapentin kinetics disposition and pharmacodynamics (PK-PD) in patients with neuropathic pain. Thus, non-diabetic patients (Control Group, n=10), patients with controlled diabetes (n=9) and patients with uncontrolled diabetes (n=10), all with neuropathic pain of intensity ≥ 4 in pain visual analog scale (0-10) were investigated.

Detailed description

Gabapentin (GBP), anticonvulsant used to neuropathic pain treatment, is mainly eliminated unchanged in urine. Renal active tubular secretion has been suggested to contribute on GBP excretion by renal excretion. Studies performed on rats with experimental diabetes suggest that hyperglycemia reduces the activity of organic cation transporters (Oct). Thus, the aim of the study was to investigate the role of OCTs on kinetic disposition and pharmacodynamics of GBP in patients with neuropathic pain and to verify the regulation of these transporters' activity by glycemic control in diabetes. A cross-over clinical study was performed in patients with neuropathic pain (n=10, Control) to evaluate the influence of CTZ on GBP kinetic disposition. To evaluate the effect of glycemic control, patients with controlled DM2 (DC, n=9) and uncontrolled DM2 (DNC, n=10) were investigated. All participants investigated had neuropathic pain of intensity ≥ 4 evaluated by analogue visual scale (EVA) and were treated with oral single-dose of 300 mg of GBP (Phase 1) or cetirizine (20 mg/day) for 5 days and single-dose of GBP on the last day (Phase 2). Only participants of Control group participated of Phase 2. Serial blood and urine samples were collected up to 36 hours after GBP administration. The intensity of pain was evaluated at the same time of blood sampling, using the visual analog scale. GBP concentration in plasma and urine was validated by JPLC-UV. All participants were genotyped for polymorphisms SLC22A2 808G\>T and SLC22A4 1507C\>T. The pharmacokinetic parameters were estimated by non-compartmental analysis.

Conditions

• Neuropathic Pain
• Type 2 Diabetes Mellitus
• Diabetic Neuropathy, Painful

Interventions

Type	Name	Description
PROCEDURE	Serial Blood Samples	Serial blood samples were collected at times 0, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 24 and 36 hours after gabapentin administration, for all patients.
PROCEDURE	Serial Urine Samples	Serial urine samples were collected at intervals 0-8 hours, 8-16 hours, 16-24 hours and 24-36 hours after gabapentin administration, for all patients.
DRUG	Gabapentin 300 mg	All patients were treated with oral single dose of gabapentin 300 mg.
DRUG	Cetirizine Hydrochloride 10 mg	Patients of control group were treated with cetirizine hydrochloride, 10 mg, twice as day, orally, for five days.

Timeline

• Start date: 2015-11-01
• Primary completion: 2018-05-01
• Completion: 2019-07-01
• First posted: 2017-02-08
• Last updated: 2019-07-05