Oncotarget

Research Papers:

Physiologically based pharmacokinetic modeling for predicting irinotecan exposure in human body

Yingfang Fan, Najia Mansoor, Tasneem Ahmad, RafeeqAlam Khan, Martin Czejka, Syed Sharib, Dong-Hua Yang and Mansoor Ahmed _

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Oncotarget. 2017; 8:48178-48185. https://doi.org/10.18632/oncotarget.18380

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Abstract

Yingfang Fan1,2,*, Najia Mansoor3,*, Tasneem Ahmad4, Rafeeq Alam Khan3, Martin Czejka5, Syed Sharib4, Dong-Hua Yang2 and Mansoor Ahmed6

1Department of Hepatobiliary Surgery, Zhujiang Hospital, Southern Medical University, Guangzhou 510280, China

2Department Pharmaceutical Sciences, College of Pharmacy and Health Sciences, St. John’s University, Queens, NY 11439, USA

3Department of Pharmacology, Faculty of Pharmacy & Pharmaceutical Sciences, University of Karachi, Karachi 75270, Pakistan

4Pharma Professional Services, Karachi 75270, Pakistan

5Department of Clinical Pharmacy and Diagnostics, University of Vienna, A-1090 Vienna, Austria

6Department of Pharmaceutical Chemistry, Faculty of Pharmacy & Pharmaceutical Sciences, University of Karachi, Karachi 75270, Pakistan

*These authors have contributed equally to this work

Correspondence to:

Mansoor Ahmed, email: cando@cyber.net.pk

Dong-Hua Yang, email: yangd1@stjohns.edu

Keywords: physiologically based pharmacokinetics (PBPK), irinotecan, colorectal cancer

Received: March 24, 2017    Accepted: May 04, 2017    Published: June 06, 2017

ABSTRACT

Colorectal cancer is the third leading cause of cancer-related deaths in the United States. Treatment of colorectal cancer remains a challenge to clinicians as well as drug developers. Irinotecan, a Camptothecin derivative, is successfully used for the treatment of this rapidly progressing malignancy and finds its place in the first line of therapeutic agents. Irinotecan is also effective in treating SCLC, malignant glioma and pancreatic adenocarcinoma. However, its adverse effects limit its clinical application. Mainly metabolized by hepatic route, and excreted through biliary tract, this dug has been found to possess high variation in patients in its pharmacokinetic (PK) profile. Physiologically based pharmacokinetic (PBPK) models using compartmental approach have attained their position to foresee the possible PK behavior of different drugs before their administration to patients and such models have been proposed for several anticancer agents. In this work, we used WB-PBPK technology to develop a model in a population of tumor patients who used IV irinotecan therapy. This model depicted the concentration of drug and its pharmacologically active metabolite in human body over a specific period of time. Knowledge about pharmacokinetic parameters is extracted from this profile and the model is evaluated by the observed results of clinical study presented in literature. The predicted behavior of the drug by this approach is in good agreement with the observed results and can aid in further exploration of PK of irinotecan in cancer patients, especially in those concomitantly suffer from other morbidity.


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