Neuropathic Pain, Type 2 Diabetes Mellitus, Diabetic Neuropathy, Painful
Conditions
Brief 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.
Interventions
PROCEDURESerial 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.
PROCEDURESerial 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.
All patients were treated with oral single dose of gabapentin 300 mg.
DRUGCetirizine Hydrochloride 10 mg
Patients of control group were treated with cetirizine hydrochloride, 10 mg, twice as day, orally, for five days.
Sponsors
University of Sao Paulo
Natalia Valadares de Moraes
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 59 Years
Healthy volunteers
No
Inclusion criteria
* Adult patients, both gender * Patients with neuropathic pain with score ≥ 4 in visual analog scale * Patients with controlled type 2 diabetes (glycated hemoglobin ≤ 8.0%) and diabetic neuropathy with score ≥ 4 in visual analog scale * Patients with uncontrolled type 2 diabetes (glycated hemoglobin ≥ 8.0%) and diabetic neuropathy with score ≥ 4 in visual analog scale * Patients that suspend the use of analgesics for 10 times half-life before starting the protocol
Exclusion criteria
* Patients with acute or chronicle severe renal failure (creatinine clearance ≤ 30 mL/min) * Patients with gastrointestinal diseases * Patients with history of alcohol and drug abuse * Patients with acute myocardial insufficiency * Patients with another kind of chronicle pain as severe as neuropathic pain * Patients in chronicle use of drugs that interact with gabapentin (antacids and cimetidine)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetic parameter (AUC) | Up to 36 hours after gabapentin (300 mg) administration | Area under the plasma concentration versus time (AUC) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetic parameter (Elimination half-life) | Up to 36 hours after gabapentin (300 mg) administration | Elimination half-life |
| Pharmacokinetic parameter (Total clearance) | Up to 36 hours after gabapentin (300 mg) administration | Total clearance |
| Pharmacokinetic parameter (Renal clearance) | Up to 36 hours after gabapentin (300 mg) administration | Renal clearance |
| Pharmacokinetic parameter (Vd) | Up to 36 hours after gabapentin (300 mg) administration | Volume of distribution (Vd) |
Outcome results
None listed