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Population pharmacokinetics of erlotinib in Japanese patients with advanced non-small cell lung cancer.

Abstract：

WHAT IS KNOWN AND OBJECTIVE:This study aimed to elucidate the pharmacokinetics of erlotinib in Japanese patients with advanced non-small cell lung cancer (NSCLC) and to investigate the relationship between erlotinib exposure and the occurrence of interstitial lung disease (ILD)-like events. METHODS:Population pharmacokinetics analysis was performed using nonlinear mixed-effects modelling software (NONMEM) based on 348 plasma samples from 97 patients obtained in two phase II clinical studies. Individual empirical Bayesian estimates (EBEs) of apparent oral clearance (CL/F) and Cmax were compared between the patients who developed and did not develop ILD-like events. RESULTS:A 1-compartment model with first-order absorption and first-order elimination was used to describe the plasma concentrations of erlotinib. The estimated population pharmacokinetics parameters were as follows: 4·71 L/h for CL/F, 163 L for apparent volume of distribution (Vc /F) and 1·97 h(-1) for absorption rate constant (Ka ). Total bilirubin (TBIL) and alpha 1-acid glycoprotein (AGP) were identified as statistically significant covariates for CL/F. No differences in CL/F and Cmax were observed between the patients with ILD-like events and those without ILD-like events. WHAT IS NEW AND CONCLUSIONS:A population pharmacokinetics model of erlotinib was developed and validated in Japanese patients. There was no relationship between exposure of erlotinib before the occurrence of ILD-like events and the occurrence of ILD-like events when erlotinib was administered at the same dosage. The high plasma concentration of erlotinib reported in patients after the onset of ILD-like events may be explained by CL/F decrease which occurs along with increasing levels of AGP which was identified as a covariate for CL/F.

journal_name

J Clin Pharm Ther

journal_title

Journal of clinical pharmacy and therapeutics

authors

Emoto-Yamamoto Y,Iida S,Kawanishi T,Fukuoka M

doi

10.1111/jcpt.12232

subject

Has Abstract

pub_date

2015-04-01 00:00:00

pages

232-9

issue

eissn

0269-4727

issn

1365-2710

journal_volume

pub_type

杂志文章

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Population pharmacokinetics of erlotinib in Japanese patients with advanced non-small cell lung cancer.