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Drug Metab Dispos. 2016 Dec;44(12):1934-1939. Epub 2016 Sep 26.

When Is It Important to Measure Unbound Drug in Evaluating Nanomedicine Pharmacokinetics?

Author information

1
Nanotechnology Characterization Laboratory, Cancer Research Technology Program, Leidos Biomedical Research, Frederick National Laboratory for Cancer Research, Frederick, Maryland (S.T.S., D.M.S.); and Food and Drug Administration, Center for Veterinary Medicine, Office of New Animal Drug Evaluation, Rockville, Maryland (M.N.M.).
2
Nanotechnology Characterization Laboratory, Cancer Research Technology Program, Leidos Biomedical Research, Frederick National Laboratory for Cancer Research, Frederick, Maryland (S.T.S., D.M.S.); and Food and Drug Administration, Center for Veterinary Medicine, Office of New Animal Drug Evaluation, Rockville, Maryland (M.N.M.) marilyn.martinez@fda.hhs.gov.

Abstract

Nanoformulations have become important tools for modifying drug disposition, be it from the perspective of enabling prolonged drug release, protecting the drug molecule from metabolism, or achieving targeted delivery. When examining the in vivo pharmacokinetic properties of these formulations, most investigations either focus on systemic concentrations of total (encapsulated plus unencapsulated) drug, or concentrations of encapsulated and unencapsulated drug. However, it is rare to find studies that differentiate between protein-bound and unbound (free) forms of the unencapsulated drug. In light of the unique attributes of these formulations, we cannot simply assume it appropriate to rely upon the protein-binding properties of the traditionally formulated or legacy drug when trying to define the pharmacokinetic or pharmacokinetic/pharmacodynamic characteristics of these nanoformulations. Therefore, this commentary explores reasons why it is important to consider not only unencapsulated drug, but also the portion of unencapsulated drug that is not bound to plasma proteins. Specifically, we highlight those situations when it may be necessary to include measurement of unencapsulated, unbound drug concentrations as part of the nanoformulation pharmacokinetic evaluation.

PMID:
27670412
PMCID:
PMC5118636
DOI:
10.1124/dmd.116.073148
[Indexed for MEDLINE]
Free PMC Article

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