Exposure-response analyses of the effects of pregabalin in patients with fibromyalgia using daily pain scores and patient global impression of change.
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.
Byon
Wonkyung
W
Clinical Pharmacology, Pfizer Global Research and Development, 50 Pequot Avenue, New London, CT 06320, USA. wonkyung.byon@Pfizer.com
Ouellet
Daniele
D
Chew
Marci
M
Ito
Kaori
K
Burger
Paula
P
Pauer
Lynne
L
Zeiher
Bernhardt
B
Corrigan
Brian
B
D000328:Adult; D000375:Aging / Q000502:physiology; D000465:Algorithms; D000700:Analgesics / Q000627:therapeutic use*; D003404:Creatinine / Q000378:metabolism; D003627:Data Interpretation, Statistical; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D005356:Fibromyalgia / Q000188:drug therapy*; D006207:Half-Life; D006801:Humans; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D015233:Models, Statistical; D017711:Nonlinear Dynamics; D010147:Pain Measurement; D000069583:Pregabalin; D012727:Sex Characteristics; D005680:gamma-Aminobutyric Acid / Q000031:analogs & derivatives* / Q000627:therapeutic use
D000700:Analgesics; D000069583:Pregabalin; D005680:gamma-Aminobutyric Acid; D003404:Creatinine