NDLI: Using Physiologically Based Pharmacokinetic (PBPK) Modeling to Evaluate the Impact of Pharmaceutical Excipients on Oral Drug Absorption: Sensitivity Analyses

Content Provider	Springer Nature Link
Author	Chow, Edwin Chiu Yuen Talattof, Arjang Tsakalozou, Eleftheria Fan, Jianghong Zhao, Liang Zhang, Xinyuan
Copyright Year	2016
Abstract	Drug solubility, effective permeability, and intestinal metabolism and transport are parameters that govern intestinal bioavailability and oral absorption. However, excipients may affect the systemic bioavailability of a drug by altering these parameters. Thus, parameter sensitivity analyses using physiologically based pharmacokinetic (PBPK) models were performed to examine the potential impact of excipients on oral drug absorption of different Biopharmaceutics Classification System (BCS) class drugs. The simulation results showed that changes in solubility had minimal impact on C$_{max}$ and AUC$_{0-t}$ of investigated BCS class 1 and 3 drugs. Changes in passive permeability altered C$_{max}$ more than AUC$_{0-t}$ for BCS class 1 drugs but were variable and drug-specific across different BCS class 2 and 3 drugs. Depending on the drug compounds for BCS class 1 and 2 drugs, changes in intestinal metabolic activity altered C$_{max}$ and AUC$_{0-t}$. Reducing or increasing influx and efflux transporter activity might likely affect C$_{max}$ and AUC$_{0-t}$ of BCS class 2 and 3 drugs, but the magnitude may be drug dependent. Changes in passive permeability and/or transporter activity for BCS class 2 and 3 drugs might also have a significant impact on fraction absorbed and systemic bioavailability while changes in intestinal metabolic activity may have an impact on gut and systemic bioavailability. Overall, we demonstrate that PBPK modeling can be used routinely to examine sensitivity of bioavailability based on physiochemical and physiological factors and subsequently assess whether biowaiver requirements need consideration of excipient effects for immediate release oral solid dosage forms.
Starting Page	1500
Ending Page	1511
Page Count	12
File Format	PDF
ISSN	12341234
Journal	The AAPS Journal
Volume Number	18
Issue Number	6
e-ISSN	15507416
Language	English
Publisher	Springer US
Publisher Date	2016-08-12
Publisher Institution	American Association of Pharmaceutical Scientists
Publisher Place	New York
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Pharmacology/Toxicology Biochemistry Biotechnology Pharmacy
Content Type	Text
Resource Type	Article

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1	Ministry of Education (GoI), Department of Higher Education	Sanctioning Authority	https://www.education.gov.in/ict-initiatives
2	Indian Institute of Technology Kharagpur	Host Institute of the Project: The host institute of the project is responsible for providing infrastructure support and hosting the project	https://www.iitkgp.ac.in
3	National Digital Library of India Office, Indian Institute of Technology Kharagpur	The administrative and infrastructural headquarters of the project	Dr. B. Sutradhar bsutra@ndl.gov.in
4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
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9	IDR Setup or Support	Queries related to establishment and support of Institutional Digital Repository (IDR) and IDR workshops	idr@ndl.gov.in

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