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Exposure‐response analysis of pregabalin add‐on treatment of patients with refractory partial seizures
Author(s) -
Miller Raymond,
Frame Bill,
Corrigan Brian,
Burger Paula,
Bockbrader Howard,
Garofalo Elizabeth,
Lalonde Richard
Publication year - 2003
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1016/s0009-9236(03)00049-3
Subject(s) - pregabalin , medicine , refractory (planetary science) , placebo , partial seizures , anesthesia , population , dosing , epilepsy , refractory period , physics , alternative medicine , environmental health , pathology , psychiatry , astrobiology
Objective : Our objectives were to describe the exposure‐response relationship of pregabalin add‐on treatment for refractory partial seizures after multiple dosing in patients and to identify the factors that influence this relationship. Methods : A mixed‐effects model was used to characterize the relationship between monthly seizure frequency over a 3‐month period and pregabalin daily dose (0, 50, 150, 300, and 600 mg) as add‐on treatment in 3 double‐blind, parallel‐group studies in patients with refractory partial seizures (N = 1042). Seizure frequency was modeled as a Poisson process expressed as a function of baseline seizures, drug treatment, placebo effect, and subject‐specific random effects. The model included a parameter that partitioned the population into subpopulations with respect to response. Results : Seventy‐five percent of patients showed an asymptotic decrease in seizure frequency with increasing doses of pregabalin, whereas 25% did not demonstrate a significant decrease in seizure frequency from baseline. In patients who demonstrated a dose‐related decrease in seizure frequency from baseline, the maximal percentage of seizure reduction from baseline was 100% for women and 80% for men, with a 186‐mg daily dose decreasing seizures on average to 50% of maximum. Age, race, and menopausal status did not significantly affect seizure frequency. Conclusion : Pregabalin add‐on treatment demonstrates a dose‐response relationship in 3 out of 4 patients with refractory partial seizures. A dose of 186 mg pregabalin daily is expected to decrease the seizure rate by 50% of maximum from baseline. Age, race, and menopausal status of women did not affect the dose‐response relationship. Clinical Pharmacology & Therapeutics (2003) 73 , 491–505; doi: 10.1016/S0009‐9236(03)00049‐3