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Pregabalin exposure‐response analysis in patients with postherpetic neuralgia
Author(s) -
Chapel S.,
Kowalski K.,
Hutmacher M.,
Bockbrader H.
Publication year - 2005
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1016/j.clpt.2004.12.228
Subject(s) - postherpetic neuralgia , pregabalin , medicine , covariate , placebo , population , regimen , anesthesia , nonmem , neuralgia , physical therapy , neuropathic pain , statistics , alternative medicine , mathematics , environmental health , pathology
Background/Aims A population exposure‐response (E‐R) analysis was performed to relate pain in postherpetic neuralgia (PHN) patients to pregabalin exposure following multiple doses. Methods Data from 4 clinical trials were combined (N=1027). Individual daily pain scores using an 11‐point numerical rating scale (0= No Pain to 10= Worst Possible Pain) were modeled as an ordered categorical variable. The doses tested included placebo, 75, 150, 300, and 600 mg/day. Covariate effects for age, gender, body weight, CLcr, average baseline pain score, and regimen (TID vs BID) were investigated to determine the impact of these factors on the E‐R relationship. Results The E‐R relationship was adequately described using a power model in dose (αD γ ) due to insufficient information to support an Emax model. Covariate selection was performed using Wald's approximation method. Gender, age, weight, and baseline pain score were influential covariates in the final model. Pain relief was adequately predicted for both regimens without inclusion of a regimen effect. Cross‐validation (external posterior predictive check) indicated the final model adequately predicts the BID regimen data even when the model parameters are estimated solely based on data from the TID regimens. Conclusions In the PHN population, the E‐R relationship indicated that 600 mg/day demonstrates increased pain relief compared to 300 mg/day. BID and TID regimens demonstrated similar efficacy. Clinical Pharmacology & Therapeutics (2005) 77 , P88–P88; doi: 10.1016/j.clpt.2004.12.228