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One Mouse, One Pharmacokinetic Profile: Quantitative Whole Blood Serial Sampling for Biotherapeutics

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Abstract

Purpose

The purpose of this study was to validate the approach of serial sampling from one mouse through ligand binding assay (LBA) quantification of dosed biotherapeutic in diluted whole blood to derive a pharmacokinetic (PK) profile.

Methods

This investigation compared PK parameters obtained using serial and composite sampling methods following administration of human IgG monoclonal antibody. The serial sampling technique was established by collecting 10 μL of blood via tail vein at each time point following drug administration. Blood was immediately diluted into buffer followed by analyte quantitation using Gyrolab to derive plasma concentrations. Additional studies were conducted to understand matrix and sampling site effects on drug concentrations.

Results

The drug concentration profiles, irrespective of biological matrix, and PK parameters using both sampling methods were not significantly different. There were no sampling site effects on drug concentration measurements except that concentrations were slightly lower in sodium citrated plasma than other matrices.

Conclusions

We recommend the application of mouse serial sampling, particularly with limiting drug supply or specialized animal models. Overall the efficiencies gained by serial sampling were 40–80% savings in study cost, animal usage, study length and drug conservation while inter-subject variability across PK parameters was less than 30%.

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Abbreviations

ACTH:

Adrenocorticotropic hormone

DBS:

Dried blood spot

HCT:

Hematocrit

IP:

Intra-peritoneal

IV:

Intravenous

LBA:

Ligand binding assay

PK:

Pharmacokinetics

PMT:

Photomultiplier tube

RO:

Retro-orbital

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Acknowledgments and Disclosures

Alison P. Joyce and Mengmeng Wang contributed equally to the preparation of this manuscript. The authors would like to thank the following individuals: Kurex Sidik, Ryan Jackobek, Todd Turner, Jennifer Spencer-Pierce, Carolyn Mallozzi, Angela Hernandez, John Harrold, Anson Abraham, Anup Zutshi, Yiqun Zhang.

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Authors and Affiliations

  1. Department of Pharmacokinetics, Dynamics and Metabolism, Pfizer, Inc., One Burtt Road, Andover, Massachusetts, 01810, USA

    Alison P. Joyce, Mengmeng Wang, Rosemary Lawrence-Henderson, Sheldon S. Leung & Denise M. O’Hara

  2. Comparative medicine, Pfizer, Inc., One Burtt Road, Andover, Massachusetts, 01810, USA

    Cynthia Filliettaz

  3. Therapeutics for Rare and Neglected Diseases Program, National Center for Translational Therapeutics National Institutes of Health, 9800 Medical Center Drive, Rockville, Maryland, 20850, USA

    Xin Xu

Authors
  1. Alison P. Joyce
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  2. Mengmeng Wang
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  3. Rosemary Lawrence-Henderson
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  4. Cynthia Filliettaz
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  5. Sheldon S. Leung
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  6. Xin Xu
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  7. Denise M. O’Hara
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Corresponding author

Correspondence to Mengmeng Wang.

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Joyce, A.P., Wang, M., Lawrence-Henderson, R. et al. One Mouse, One Pharmacokinetic Profile: Quantitative Whole Blood Serial Sampling for Biotherapeutics. Pharm Res 31, 1823–1833 (2014). https://doi.org/10.1007/s11095-013-1286-y

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  • DOI: https://doi.org/10.1007/s11095-013-1286-y

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