Exposure-response analyses of the effects of pregabalin in patients with
fibromyalgia using daily pain scores and patient global impression of change.
Author(s): Byon W, Ouellet D, Chew M, Ito K, Burger P, Pauer L, Zeiher B, Corrigan B.
Affiliation(s): Clinical Pharmacology, Pfizer Global Research and Development, 50 Pequot Avenue,
New London, CT 06320, USA. wonkyung.byon@Pfizer.com
Publication date & source: 2010, J Clin Pharmacol. , 50(7):803-15
Data from 4 phase 2/3 studies were pooled to characterize the exposure response
of daily pregabalin (150-600 mg) in patients with fibromyalgia using
self-assessed daily pain scores (PAIN) and end-of-treatment patient global
impression of change (PGIC). The exposure responses of both endpoints were
characterized by an Emax model using nonlinear mixed-effects modeling (NONMEM).
Drug effect on PAIN relative to placebo was significant with additional maximum
effect of 1.51 points on the logit scale and EC50 of 1.54 ng/mL (dose of 174 mg)
and a rapid onset (half-life of 11 hours), consistent with the half-life of the
drug. The decrease in PAIN with placebo occurred more slowly, reaching maximum
response (1.52 points on the logit scale) after 1 month. Drug response in
fibromyalgia was dependent on age and sex, with greater PAIN reduction in older
patients, in addition to the effect of creatinine clearance, and in females. For
PGIC, administration of pregabalin resulted in an increase in the proportion of
patients reporting improvement with an ED50 of 228 mg. The analyses support the
recommended dose of pregabalin in patients with fibromyalgia of 300 to 450 mg/d.