A Physiologically‐Based Pharmacokinetic Model for the Prediction of Monoclonal Antibody Pharmacokinetics From In Vitro Data

Monoclonal antibody (mAb) pharmacokinetics (PK) have largely been predicted via allometric scaling with little consideration for cross‐species differences in neonatal Fc receptor (FcRn) affinity or clearance/distribution mechanisms. To address this, we developed a mAb physiologically‐based PK model that describes the intracellular trafficking and FcRn recycling of mAbs in a human FcRn transgenic homozygous mouse and human. This model uses mAb‐specific in vitro data together with species‐specific FcRn tissue expression, tissue volume, and blood‐flow physiology to predict mAb in vivo linear PK a priori. The model accurately predicts the terminal half‐life of 90% of the mAbs investigated within a twofold error. The mechanistic nature of this model allows us to not only predict linear PK from in vitro data but also explore the PK and target binding of mAbs engineered to have pH‐dependent binding to its target or FcRn and could aid in the selection of mAbs with optimal PK and pharmacodynamic properties.

• Publication year

  2019

• Venue

  CPT: Pharmacometrics & Systems Pharmacology

• Publication date

  2019-09-23

• Fields of study

  Medicine, Chemistry

• Identifiers
  DOI 10.1002/psp4.12461PMID 31464379PMCID 6813168
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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