2006 - Brugge/Bruges - Belgium

PAGE 2006: Applications- CNS
Raymond Miller

Comparision of Pregabalin and Gabapentin Pharmacodynamics in Patients with Refractory Partial Seizures.

Miller, Raymond , Howard Bockbrader, Sunny Chapel.

Pfizer Global Research and Development, Ann Arbor, USA

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Objective: To compare the dose-response (seizure frequency) relationship of pregabalin and gabapentin add-on treatment in patients with refractory partial epilepsy.

Background: Pregabalin (Lyrica®) and gabapentin (Neurontin®) are antiepileptic drugs that appear to have a similar mechanism of action through binding to the α2-δ subunit of voltage-gated calcium channels. Preclinical studies with pregabalin and gabapentin indicate similar anticonvulsant pharmacological profiles; however, pregabalin shows 3- to 6-fold greater potency. Pregabalin, unlike gabapentin, exhibits linear absorption with observed maximum plasma drug concentration (Cmax) and area under the plasma drug concentration-time profile (AUC) increasing proportionally with dose. In contrast, the extent of gabapentin absorption decreases with increasing dose. 

Methods: Data from 3 pregabalin clinical trials (1042 patients) and 6 gabapentin trials (551 patients) were analyzed using a nonlinear mixed-effects model to characterize the relationship between seizure frequency and pregabalin and gabapentin dose. Percent of responders among patients was estimated.

Results: Pregabalin (50–600 mg/d) and gabapentin (600–1800 mg/d) showed an asymptotic dose-related decrease in seizure frequency. Both pregabalin- and gabapentin-treated patients demonstrated a dose-response relationship; however, the maximal decrease in seizure frequency from baseline with pregabalin was 100%, while the maximal decrease with gabapentin therapy was 24.5%. Based on this information, pregabalin was estimated to be 4 times more effective than gabapentin in patients who responded to treatment. Pregabalin was also 2.5 times more potent than gabapentin in responding patients, as measured by the dose that reduced seizure frequency by 50%.

Conclusions: The observed improvement in potency and effectiveness combined with the pharmacokinetic-pharmacodynamic properties of pregabalin relative to gabapentin offer distinct advantages over standard gabapentin therapy for the treatment of refractory partial seizures.

Reference: PAGE 15 (2006) Abstr 941 [www.page-meeting.org/?abstract=941]
Poster: Applications- CNS