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标题：Population pharmacokinetics of vedolizumab in Asian and non-Asian patients with ulcerative colitis and Crohn’s disease
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作者：Hiroyuki Okamoto ; Nathanael L. Dirks ; Maria Rosario 等
期刊名称：Intestinal Research
印刷版ISSN：1598-9100
电子版ISSN：2288-1956
出版年度：2021
卷号：19
期号：1
页码：95-105
DOI：10.5217/ir.2019.09167
出版社：Korean Association for the Study of Intestinal Diseases
摘要：Background/Aims Vedolizumab is indicated for moderately-to-severely active ulcerative colitis (UC) and Crohn’s disease (CD). Because multiple factors may result in different pharmacokinetics and clinical efficacies, understanding determinants of vedolizumab clearance may enhance dose and treatment strategies. The aim was to characterize vedolizumab pharmacokinetics in Asian and non-Asian UC and CD patients. Methods Population pharmacokinetic analysis for repeated measures, using data from 5 studies, was conducted using nonlinear mixed-effects modeling. A Bayesian estimation approach in NONMEM 7.3 was utilized to leverage the predominantly sparse data available for this analysis with results from a prior population pharmacokinetic analysis of vedolizumab. Results Vedolizumab pharmacokinetics were described by a 2-compartment model with parallel linear and nonlinear elimination. Using reference covariate values, linear elimination half life of vedolizumab was 24.7 days for anti-vedolizumab antibody (AVA)-negative patients and 18.1 days for AVA-positive patients; linear clearance (CL L ) was 0.165 L/day for AVA-negative patients and 0.246 L/day for AVA-positive patients; central (V c ) and peripheral compartment volumes of distribution were 3.16 L and 1.84 L, respectively. Interindividual variabilities (percent coefficient of variation) were 30.8% for CL L and 19% for V c ; interoccasion variability on CL L was 20.3%; residual variance was 17.8%. For albumin, body weight and AVA, only extreme values were identified as potentially clinically important predictors of CL L . The effect of race (Asian/non-Asian) and diagnosis (UC/CD) on CL L was negligible and likely not of clinical importance. Conclusions Pharmacokinetic parameters were similar in Asian and non-Asian patients with moderately-to-severely active UC and CD. This analysis supports use of vedolizumab flat-fixed dosing in these patients.
关键词：Population pharmacokinetics; Vedolizumab; Colitis; ulcerative; Crohn disease; Asian