Effects of therapeutic doses of Pregabalin on QTc interval in conscious rabbits

Eur Rev Med Pharmacol Sci. Jul-Aug 2008;12(4):223-8.

Abstract

Pregabalin (PRG) is a new antiepileptic drug that has been used as supportive therapy for partial seizures in patients. Although many neuro-psychiatric and non-cardiac drugs are known to prolong ventricular repolarization as manifested by QTc prolongation on ECG of which provokes torsades de pointes, there is limited data available regarding the characteristics of QT interval in conscious laboratory animals after PRG administration. For that purpose, effects of different therapeutic doses of oral PRG administration on Heart Rate (HR), QT and QTc values in rabbits were evaluated at a predefined time interval in this research. The study involved 28 New Zealand rabbits of both sexes, aged between 8 and 12 months. Animals were divided into four equal groups. Rabbits in control group (CG) received saline 0.5 ml/per animal orally. Group I, II and III were orally given single dose of PRG at 1.25 mg/kg, 2.5 mg/kg and 5 mg/kg, respectively. ECG records were taken before experiment (baseline) and at 1st, 2nd, 4th, and 6th hour (h) of experiment by direct writing electrocardiograph. HR, QT and QTc values were determined from ECG records. Heart rates increased in all groups when compared to baseline values. The increases were evident at 4th h in group II (p < 0.001), at 2nd h (p < 0.05) and 4th h (p < 0.001) in group III compared with CG. After application of PRG, QTc began to prolong at 1st h through the 4th of experiment and then turned to baseline values at 6th h of the experiment. The QTc values obtained at 2nd h in Group II and III (p < 0.05) and 4th h (p < 0.001) of application in group III were significantly different from CG. Changes obtained in HR, QT and QTc values in PRG treated rabbits were time and dose dependent (p < 0.001). Increase in HR and QTc prolongation determined in PRG given rabbits may implied that clinicians should take care of these changes when using this drug and further studies are required to fully understand the mechanism involved.

MeSH terms

  • Administration, Oral
  • Animals
  • Anticonvulsants / administration & dosage
  • Anticonvulsants / adverse effects*
  • Dose-Response Relationship, Drug
  • Electrocardiography
  • Female
  • Heart Rate / drug effects*
  • Long QT Syndrome / chemically induced*
  • Male
  • Pregabalin
  • Rabbits
  • Time Factors
  • gamma-Aminobutyric Acid / administration & dosage
  • gamma-Aminobutyric Acid / adverse effects
  • gamma-Aminobutyric Acid / analogs & derivatives*

Substances

  • Anticonvulsants
  • Pregabalin
  • gamma-Aminobutyric Acid