Clinical pharmacology and therapeutics · 2003
Exposure-response analysis of pregabalin add-on treatment of patients with refractory partial seizures.
Клиническое исследованиеСтатьяМногоцентровое исследованиеРандомизированное исследованиеНазвание и аннотация: Перевод в очереди
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Miller Raymond, Frame Bill, Corrigan Brian, Burger Paula, Bockbrader Howard, Garofalo Elizabeth, Lalonde Richard
Аннотация
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.
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.