Relationship Between Plasma Levels and the Anti-Neuropathic Pain Effect of Lamotrigine in Rats

Abstract

The purpose of this study was to assess the concentration-analgesic effect on neuropathic pain relationship of lamotrigine (LMT) from the direct plasma studies and pharmacodynamic studies. Although the anticonvulsant drugs are used for neuropathy, their pharmacokinetic and pharmacodynamic correlation on the time course of the effect of two drugs was determined after oral administration in conjunction with their pharmacokinetics. Non-compartmental analysis was adopted to calculate pharmacokinetics of the drug. Neuropathic pain was induced by chronic constriction injury of sciatic nerve. This technique allows consecutive measurements of the paw withdrawal thresholds and paw withdrawal duration on hyperalgesia and allodynia, respectively. Increase in threshold and decrease in duration of paw withdrawals were used as analgesic effect against neuropathy. After administration of drug, pronounced reversal in pain could be observed from all the behavioral studies and pharmacokinetic-pharmacodynamic studies showed good correlation coefficient which indicated a positive correlation. Findings from the current, preclinical study showed good relation between pharmacokinetics and pharmacodynamics of anticonvulsants on neuropathy.

Keywords: Lamotrigine, neuropathy, pharmacokinetics, pharmacodynamics