NDLI: Are hepatic impairment studies necessary for therapeutic proteins?

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Yang, Jun Shord, Stacy Zhao, Hong Men, Yuxin Rahman, Atiqur
Spatial Coverage	United States
Description	Author Affiliation: Yang J ( Office of Clinical Pharmacology, Office of Translational Sciences, US Food and Drug Administration, Silver Spring, Maryland. Electronic address: jun.yang@fda.hhs.gov.)
Abstract	OBJECTIVE: This study assessed whether trials to investigate the effect of hepatic impairment on the pharmacokinetics of therapeutic proteins (TPs), which are conducted for small molecule drugs, are necessary. METHODS: The product labeling for 91 TPs that have been approved by the US Food and Drug Administration were reviewed. A PubMed search was also conducted to identify completed studies that assessed the effect of hepatic impairment on the pharmacokinetics of TPs. Biologic License Applications were subsequently reviewed to gather further descriptions of the trials conducted in patients with hepatic impairment and data analyses. RESULTS: No dedicated pharmacokinetics trials were conducted in patients with hepatic impairment for these approved TPs, but subgroup (n = 2 [2.2%]) or population (n = 5 [5.5%]) pharmacokinetic analyses were performed for 7 TPs. The pharmacokinetics of these proteins were not affected by the hepatic dysfunction, with the exception that the clearance of drotrecogin alfa seemed 25% higher in patients with hepatic impairment than in patients without hepatic impairment; however, no dose reduction was recommended. Thus, the effect of hepatic impairment on the pharmacokinetics of TPs is unclear based on the limited analyses completed to date. CONCLUSIONS: A dedicated pharmacokinetics trial for TPs in patients with hepatic impairment is not necessary. Recognizing that the data are very limited, it would be important to continue collecting pharmacokinetic data of TP in patients with hepatic impairment and using population pharmacokinetic analyses to evaluate the effect of hepatic impairment on the pharmacokinetics of TP.
File Format	HTM / HTML
ISSN	01492918
Issue Number	9
Volume Number	35
e-ISSN	1879114X
Journal	Clinical Therapeutics
Language	English
Publisher	Elsevier
Publisher Date	2013-09-01
Publisher Place	United States
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Discipline Pharmacology Liver Diseases Metabolism Proteins Pharmacokinetics Antibodies, Monoclonal Clinical Trials As Topic Cytokines Enzymes Therapeutic Use Humans Immunotoxins Molecular Targeted Therapy Single-chain Antibodies United States United States Food And Drug Administration Journal Article
Content Type	Text
Resource Type	Article
Subject	Pharmacology Pharmacology (medical)

Sl.	Authority	Responsibilities	Communication Details
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
5	Website/Portal (Helpdesk)	Queries regarding NDLI and its services	support@ndl.gov.in
6	Contents and Copyright Issues	Queries related to content curation and copyright issues	content@ndl.gov.in
7	National Digital Library of India Club (NDLI Club)	Queries related to NDLI Club formation, support, user awareness program, seminar/symposium, collaboration, social media, promotion, and outreach	clubsupport@ndl.gov.in
8	Digital Preservation Centre (DPC)	Assistance with digitizing and archiving copyright-free printed books	dpc@ndl.gov.in
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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