Abstracts

Interactions between antiepileptic drugs (AEDs) and oral contraceptives (OCs) can decrease the anticonvulsant effectiveness of AEDs (breakthrough seizures) as well as the contraceptive properties of OC (breakthrough bleeding or contraceptive failure). Using population pharmacokinetic (PK) and pharmacodynamic (PD) analyses on a large patient cohort formed by combining 3 clinical trials, interactions between pregabalin (PGB) and an OC were investigated. PGB is an alpha-2-delta ligand with anticonvulsant, analgesic, and anxiolytic properties that in clinical trials has been found to be an efficacious adjunct treatment for partial seizures with/without secondary generalization. PGB[apos]s PK and PD characteristics were studied using data from 3 randomized, double-blind, placebo-controlled trials consisting of an 8-wk baseline phase and a 12-wk treatment phase. Included in the PK analysis were subjects from 5 clinical pharmacology studies and 1 Phase-II study. The PK analysis assessed similarity in PGB[apos]s PK between healthy volunteers and patients with partial seizures and effect of OC on PGB[apos]s PK in females. The exposure-response (seizure frequency) relationship of PGB add-on treatment in patients with refractory partial seizures was determined using a population approach and assessed factors (eg, OC) that may influence the PD relationship. Not all patients in the PD analysis were included in the PK analysis because of exclusion criteria associated with steady state condition, dosing and/or concentration information. PGB[apos]s PK characteristics were investigated in 748 subjects (123 participated in clinical pharmacology studies and 625 participated in pivotal epilepsy efficacy trials). Of the 625 patients, 323 were females (23 were on a concomitant OC). Population PK analyses showed that the pharmacokinetics of PGB were similar in healthy volunteers and in patients with epilepsy receiving concomitant AEDs. OC use did not significantly change PGB[apos]s PK characteristics. PGB[apos]s PD characteristics were studied in 1042 patients (525 were female; 31 were on a concomitant OC). 75% of patients experienced a decrease in seizure frequency with increasing doses of PGB while 25% of patients did not exhibit significant reductions in seizure frequency. Of the patients who responded to treatment, the maximum reduction in baseline seizure frequency was 100% for women on an OC, 85.2% for women not taking an OC, and 69.8% for men. Across the study population, a daily PGB dose of 185mg decreased baseline seizure frequency by 50%. PGB is an anticonvulsant that in clinical trials has been found to be efficacious adjunct treatment for partial seizures with/without secondary generalizations. Analysis of a large cohort of patients formed by combining data from 3 clinical trials revealed that the PK and PD characteristics of PGB are not significantly affected by the use of OC. (Supported by Pfizer Inc.)