Exposure-response analysis of pregabalin add-on treatment of patients with refractory partial seizures.
Clin Pharmacol Ther
; 73(6): 491-505, 2003 Jun.
Article
em En
| MEDLINE
| ID: mdl-12811359
ABSTRACT
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.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Epilepsias Parciais
/
Ácido gama-Aminobutírico
/
Anticonvulsivantes
Tipo de estudo:
Clinical_trials
/
Prognostic_studies
Limite:
Adult
/
Female
/
Humans
/
Male
Idioma:
En
Ano de publicação:
2003
Tipo de documento:
Article