Exposure-response analysis of pregabalin add-on treatment of patients with refractory partial seizures
| Autor: | Raymond Miller, Howard Norman Bockbrader, E. A. Garofalo, Richard L. Lalonde, Bill Frame, Paula Burger, Brian Corrigan |
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| Rok vydání: | 2003 |
| Předmět: |
Adult
Male medicine.medical_treatment Population Pregabalin Drug Resistance Placebo Models Biological law.invention Epilepsy Randomized controlled trial Refractory law Medicine Humans Pharmacology (medical) Poisson Distribution education gamma-Aminobutyric Acid Pharmacology education.field_of_study Dose-Response Relationship Drug business.industry medicine.disease Dose–response relationship Anticonvulsant Treatment Outcome Research Design Anesthesia Anticonvulsants Female Epilepsies Partial business Algorithms medicine.drug |
| Zdroj: | Clinical pharmacology and therapeutics. 73(6) |
| ISSN: | 0009-9236 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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