Abstract | BACKGROUND: PATIENTS AND METHODS: We analyzed the PK of erlotinib and OSI-420 on days 1 and 8 after beginning erlotinib therapy in 9 patients with MPE. Their concentrations were determined by high-performance liquid chromatography with ultraviolet detection. Blood samples were obtained five times per day: before administration, and 2, 4, 8, and 24 hours after administration. Pleural effusions were obtained once per day, 2 hours after administration on day 1, and before administration on day 8. The exceptions were cases 2 and 4, which had pleural effusions obtained just before drug administration, and 2, 4, 8, and 24 hours after administration. RESULTS: The mean percentage of penetration from plasma to pleural effusion for erlotinib was 18% on day 1 and 112% on day 8, while these values for OSI-420 were 9.5% on day 1 and 131% on day 8. The area under the drug concentration-time curve of pleural fluid for erlotinib was 28,406 ng-hr/mL for case 2 and 45,906 ng-hr/mL for case 4. CONCLUSIONS: There seems to be a significant accumulation of both erlotinib and OSI-420 in MPE with repeated dosing. Although larger studies will be necessary to determine the true impact of erlotinib MPE accumulation on plasma PK and safety, erlotinib can be administered safely to patients with MPE with respect to efficacy and side effects.
|
Authors | Katsuhiro Masago, Yosuke Togashi, Masahide Fukudo, Tomohiro Terada, Kaoru Irisa, Yuichi Sakamori, Young Hak Kim, Tadashi Mio, Ken-Ichi Inui, Michiaki Mishima |
Journal | Clinical lung cancer
(Clin Lung Cancer)
Vol. 12
Issue 5
Pg. 307-12
(Sep 2011)
ISSN: 1938-0690 [Electronic] United States |
PMID | 21775215
(Publication Type: Clinical Trial, Journal Article)
|
Copyright | Copyright © 2011. Published by Elsevier Inc. |
Chemical References |
- OSI-420
- Protein Kinase Inhibitors
- Quinazolines
- Erlotinib Hydrochloride
|
Topics |
- Aged
- Aged, 80 and over
- Area Under Curve
- Carcinoma, Non-Small-Cell Lung
(drug therapy, pathology)
- Chromatography, High Pressure Liquid
- Erlotinib Hydrochloride
- Female
- Humans
- Lung Neoplasms
(drug therapy, pathology)
- Male
- Middle Aged
- Pleural Effusion
(metabolism)
- Protein Kinase Inhibitors
(administration & dosage, pharmacokinetics, therapeutic use)
- Quinazolines
(administration & dosage, pharmacokinetics, therapeutic use)
- Time Factors
|