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Population‐Based Pharmacokinetic and Exposure‐Efficacy Analyses of Peginterferon Beta‐1a in Patients With Relapsing Multiple Sclerosis
Author(s) -
Hu Xiao,
Hang Yaming,
Cui Yue,
Zhang Jie,
Liu Shifang,
Seddighzadeh Ali,
Deykin Aaron,
Nestorov Ivan
Publication year - 2017
Publication title -
the journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.92
H-Index - 116
eISSN - 1552-4604
pISSN - 0091-2700
DOI - 10.1002/jcph.883
Subject(s) - pharmacokinetics , dosing , medicine , volume of distribution , population , regimen , poisson regression , placebo , pharmacology , environmental health , alternative medicine , pathology
Peginterferon beta‐1a reduced annualized relapse rate as compared with placebo and was approved to treat multiple sclerosis patients. A population pharmacokinetic and an exposure‐efficacy model were developed to establish the quantitative relationship between pharmacokinetics and annualized relapse rate. The pharmacokinetics was well described by a 1‐compartment model with first‐order absorption and linear elimination kinetics. Body mass index was the most significant covariate that impacted both clearance and volume of distribution, which in turn impacted area under the curve and maximum serum concentration. Cumulative monthly area under the curve and annualized relapse rate were best described by a Poisson‐gamma (negative binomial) model, demonstrating that the improved efficacy of every‐2‐weeks dosing was driven by greater drug exposure. The results supported the superior efficacy of the every‐2‐week dosing regimen compared with the every‐4‐weeks dosing regimen.