Transporters for Organic Cations and Glycemic Control in Patients With Neuropathic Pain.
Condition: Neuropathic Pain; Type 2 Diabetes Mellitus; Diabetic Neuropathy, Painful
MeSH terms: Neuralgia; Diabetic Neuropathies; Diabetes Mellitus, Type 2
Study type: Interventional
Phase: Phase 4

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.
    

Intervention name(s): Serial Blood Samples; Serial Urine Samples; Gabapentin 300 mg; Cetirizine Hydrochloride 10 mg
Intervention type(s): Procedure; Procedure; Drug; Drug
Intervention description(s): 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.; 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.; Patients of control group were treated with cetirizine hydrochloride, 10 mg, twice as day, orally, for five days.
Intervention MeSH terms: Cetirizine; Gabapentin
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment