Albumin as a versatile platform for drug half-life extension

Sleep, Darrell; Cameron, Jason; Evans, Leslie

doi:10.1016/j.bbagen.2013.04.023

Cited by 394 publications

(346 citation statements)

References 99 publications

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“…Some drug molecules are rapidly excreted from the circulation, resulting in lower therapeutic efficacies. In this regard, albumin plays a role in increasing plasma half-life through noncovalent interaction with the small molecules (Sleep et al, 2013). Protein-drug binding may affect pharmacokinetic behaviors, including the half-life of a drug (Tayman et al, 2011).…”

Section: Resultsmentioning

confidence: 99%

Metabolite Profiling and Pharmacokinetic Evaluation of Hydrocortisone in a Perfused Three-Dimensional Human Liver Bioreactor

et al. 2015

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Endotoxin lipopolysaccharide (LPS) is known to cause liver injury primarily involving inflammatory cells such as Kupffer cells, but few in vitro culture models are applicable for investigation of inflammatory effects on drug metabolism. We have developed a threedimensional human microphysiological hepatocyte-Kupffer cell coculture system and evaluated the anti-inflammatory effect of glucocorticoids on liver cultures. LPS was introduced to the cultures to elicit an inflammatory response and was assessed by the release of proinflammatory cytokines, interleukin 6 and tumor necrosis factor a. A sensitive and specific reversed-phase-ultra high-performance liquid chromatography-quadrupole time of flightmass spectrometry method was used to evaluate hydrocortisone disappearance and metabolism at near physiologic levels. For this, the systems were dosed with 100 nM hydrocortisone and circulated for 2 days; hydrocortisone was depleted to approximately 30 nM, with first-order kinetics. Phase I metabolites, including tetrahydrocortisone and dihydrocortisol, accounted for 8-10% of the loss, and 45-52% consisted of phase II metabolites, including glucuronides of tetrahydrocortisol and tetrahydrocortisone. Pharmacokinetic parameters, i.e., half-life, rate of elimination, clearance, and area under the curve, were 23.03 hours, 0.03 hour 21 , 6.6 3 10 25 l×hour 21, and 1.03 (mg/l)*h, respectively. The ability of the bioreactor to predict the in vivo clearance of hydrocortisone was characterized, and the obtained intrinsic clearance values correlated with human data. This system offers a physiologically relevant tool for investigating hepatic function in an inflamed liver.

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Section: Resultsmentioning

confidence: 99%

Metabolite Profiling and Pharmacokinetic Evaluation of Hydrocortisone in a Perfused Three-Dimensional Human Liver Bioreactor

et al. 2015

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“…This bottleneck may be overcome by the use of HSA as a carrier to increase the circulatory half-life and bioavailability of such molecules. Strategies to achieve this may be by association, chemical conjugation, or genetic fusion to HSA (3)(4)(5).…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, albumin has a serum half-life of nearly 3 weeks in humans. This feature is of great interest to the pharmaceutical industry, as the exceptional half-life can be utilized to extend the serum persistence of therapeutics that are chemically or genetically linked to albumin (3)(4)(5). Examples are biopharmaceuticals such as cytokines, hormones, and antibody fragments.…”

Section: Albumin Is An Abundant Blood Protein That Acts As a Transpormentioning

confidence: 99%

“…Examples are biopharmaceuticals such as cytokines, hormones, and antibody fragments. Also small albumin binding scaffolds, peptides, or fatty acids fused or conjugated directly to a drug of interest, which target or associate with albumin when injected into the bloodstream, are used to improve pharmacokinetics (3)(4)(5)(6).…”

Section: Albumin Is An Abundant Blood Protein That Acts As a Transpormentioning

confidence: 99%

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Interaction with Both Domain I and III of Albumin Is Required for Optimal pH-dependent Binding to the Neonatal Fc Receptor (FcRn)

Sand

Bern

Nilsen

et al. 2014

Journal of Biological Chemistry

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“…There are broad clinical applications for biotherapeutic drug development that involve targeting FcRn due to its function in the half-life extension of albumin or Fc-fusion proteins, and monoclonal antibodies, 35,36 including delivery of therapeutic modalities via pulmonary adsorption. 37 Other applications that have been extensively studied include intravenous immunoglobulin administration for autoimmune disease by saturating FcRn to reduce the level of circulating autoantibodies, 38 and evaluation of the risk on off-target toxicities of antibody-drug conjugate by antigen-independent internalization via FcRn into lysosomes.…”

mentioning

confidence: 99%

Tissue expression profile of human neonatal Fc receptor (FcRn) in Tg32 transgenic mice

Fan

Avery

Wang

et al. 2016

mAbs

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Albumin as a versatile platform for drug half-life extension

Cited by 394 publications

References 99 publications

Metabolite Profiling and Pharmacokinetic Evaluation of Hydrocortisone in a Perfused Three-Dimensional Human Liver Bioreactor

Metabolite Profiling and Pharmacokinetic Evaluation of Hydrocortisone in a Perfused Three-Dimensional Human Liver Bioreactor

Interaction with Both Domain I and III of Albumin Is Required for Optimal pH-dependent Binding to the Neonatal Fc Receptor (FcRn)

Tissue expression profile of human neonatal Fc receptor (FcRn) in Tg32 transgenic mice

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