Drug accumulation dynamics designates the quantitative description of how intracellular drug concentration evolves over time as a net balance between drug entry and exit rates. Drug enters via passive diffusion or carrier-mediated uptake, while removal occurs through passive leakage and active efflux transporters such as P-glycoprotein [1][2][3]. Under given conditions, these opposing processes approach a steady-state intracellular concentration at which entry equals removal [2][3]. The kinetic description comprises uptake and efflux rate constants, the transmembrane concentration gradient, intracellular binding capacity, and efflux pump saturation kinetics [4]. Within drug transport and resistance mechanisms, the concept is defined by its explanatory role: acquired resistance in cancer cells is frequently characterised by reduced steady-state intracellular drug accumulation, arising from diminished uptake or enhanced efflux capacity [2]. The term thus designates the formal, rate-based account of intracellular drug exposure—spanning influx, efflux, binding, and approach to steady state—as the kinetic determinant of cytotoxic response and resistance [1][2].
- intracellular exposure
- lysosomal sequestration
- drug efflux
- tissue retention
Drug Transport and Resistance Mechanisms·Oncology·Medicine·Health Sciences
References
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- Yuchun Chen; Megan Chiem; Nandini Joshi; Paul C. H. Li; Real-Time Single-Cell Measurement and Kinetic Modeling of Daunorubicin Uptake in Multidrug-Resistant Leukemia Cells Using a Microfluidic Biochip. Pathophysiology 2026, 33, 28. [CrossRef]
- Priyanka Rani; Pranabesh Mandal; Bikash Kumar Rajak; Durg Vijay Singh; A review on dynamics of permeability-glycoprotein in efflux of chemotherapeutic drugs. Front. Drug Discov. 2024, 4, 1363364. [CrossRef]
- Valentin V. Rybenkov; Helen I. Zgurskaya; Chhandosee Ganguly; Inga V. Leus; Zhen Zhang; Mohammad Moniruzzaman; The Whole Is Bigger than the Sum of Its Parts: Drug Transport in the Context of Two Membranes with Active Efflux. Chem. Rev. 2021, 121, 5597-5631. [CrossRef]