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J Clin Pharmacol. 2014 May;54(5):593-601. doi: 10.1002/jcph.240. Epub 2013 Dec 6.

Utility of population pharmacokinetic modeling in the assessment of therapeutic protein-drug interactions.

Author information

1
Quantitative Pharmacology, Department of Pharmacokinetics & Drug Metabolism, Amgen, Inc., Thousand Oaks, CA, USA.
2
Office of Clinical Pharmacology & Office of Translational Sciences, Center for Drug Evaluation and Research, Food and Drug Administration (FDA), Silver Spring, MD, USA.
3
Exploratory Clinical and Translational Research, Bristol-Myers Squibb, Lawrenceville, NJ, USA.
4
PK/PD and Drug Metabolism, Merck & Co, West Point, PA, USA.
5
Biologics Clinical Pharmacology, Janssen Research and Development LLC, Spring House, PA, USA.
6
Clinical Pharmacology, Oncology Business Unit, Pfizer, La Jolla, CA, USA.

Abstract

Assessment of pharmacokinetic (PK) based drug-drug interactions (DDI) is essential for ensuring patient safety and drug efficacy. With the substantial increase in therapeutic proteins (TP) entering the market and drug development, evaluation of TP-drug interaction (TPDI) has become increasingly important. Unlike for small molecule (e.g., chemical-based) drugs, conducting TPDI studies often presents logistical challenges, while the population PK (PPK) modeling may be a viable approach dealing with the issues. A working group was formed with members from the pharmaceutical industry and the FDA to assess the utility of PPK-based TPDI assessment including study designs, data analysis methods, and implementation strategy. This paper summarizes key issues for consideration as well as a proposed strategy with focuses on (1) PPK approach for exploratory assessment; (2) PPK approach for confirmatory assessment; (3) importance of data quality; (4) implementation strategy; and (5) potential regulatory implications. Advantages and limitations of the approach are also discussed.

KEYWORDS:

TP–drug interaction; confirmatory PPK approach; drug–drug interaction; population pharmacokinetic model; therapeutic protein

PMID:
24272952
DOI:
10.1002/jcph.240
[Indexed for MEDLINE]
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