Introduction to Single‐Cell Physiologically‐Based Pharmacokinetic (scPBPK) Models

Abstract

The current investigation introduces single‐cell physiologically based pharmacokinetic (scPBPK) models to gain insight into drug disposition at the cellular scale. The transition from standard PBPK (sPBPK) models to scPBPK models required depiction of expression‐dependent (ED) processes, such as drug metabolism or membrane transport. ED processes utilize weighting functions—a defined or data‐driven distribution—that yield heterogeneity in individual cell kinetics. Two scPBPK model examples are provided, one involving a drug (AZD1775) subject to three ED blood–brain barrier transport processes, and another drug (midazolam) with a single ED process of metabolism by hepatocytes. For both examples, the weighting function for each ED process was defined by a negative binomial distribution that is often used in scRNAseq analytics. The AZD1775 model simulations indicated a large degree of single‐cell drug concentration heterogeneity, whereas those for midazolam did not due to high membrane transport relative to metabolism. scPBPK models offer a means to probe cellular pharmacokinetics compatible with modern omic technologies and may be extended to pharmacodynamic models.

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BibTeX RIS

BibTeX

@article{saini2026introduction,
  title = {{Introduction to Single‐Cell Physiologically‐Based Pharmacokinetic (scPBPK) Models}},
  author = {Anshul Saini and James M. Gallo},
  journal = {CPT: Pharmacometrics \& Systems Pharmacology},
  year = {2026},
  month = aug,
  doi = {10.1002/psp4.70320},
  url = {https://doi.org/10.1002/psp4.70320},
  note = {CC BY-NC 4.0},
}

RIS

TY  - JOUR
TI  - Introduction to Single‐Cell Physiologically‐Based Pharmacokinetic (scPBPK) Models
AU  - Anshul Saini
AU  - James M. Gallo
PY  - 2026
DA  - 2026/08/20
JO  - CPT: Pharmacometrics & Systems Pharmacology
DO  - 10.1002/psp4.70320
UR  - https://doi.org/10.1002/psp4.70320
AB  - The current investigation introduces single‐cell physiologically based pharmacokinetic (scPBPK) models to gain insight into drug disposition at the cellular scale. The transition from standard PBPK (sPBPK) models to scPBPK models required depiction of expression‐dependent (ED) processes, such as drug metabolism or membrane transport. ED processes utilize weighting functions—a defined or data‐driven distribution—that yield heterogeneity in individual cell kinetics. Two scPBPK model examples are provided, one involving a drug (AZD1775) subject to three ED blood–brain barrier transport processes, and another drug (midazolam) with a single ED process of metabolism by hepatocytes. For both examples, the weighting function for each ED process was defined by a negative binomial distribution that is often used in scRNAseq analytics. The AZD1775 model simulations indicated a large degree of single‐cell drug concentration heterogeneity, whereas those for midazolam did not due to high membrane transport relative to metabolism. scPBPK models offer a means to probe cellular pharmacokinetics compatible with modern omic technologies and may be extended to pharmacodynamic models.
SN  - 2163-8306
ER  -

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