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Stochastic Chiral Pharmacokinetics: Dynamics with Dual Randomized Dosing Regimens
Ze Wang1, Dingding Yan2, Xiaotian Wu3
1School of Science, Shanghai Maritime University, Shanghai, 201306, People's Republic of China.
Bulletin of Mathematical Biology
|August 14, 2026
Summary
Medication non-adherence causes significant fluctuations in chiral drug concentrations, impacting therapeutic efficacy. This study models these effects, revealing critical discrepancies between active and total drug levels.
Area of Science:
- Pharmacokinetics
- Pharmacodynamics
- Medicinal Chemistry
Background:
- Medication non-adherence critically affects drug efficacy and safety.
- The impact of non-adherence on chiral drug concentration variability, particularly enantiomeric fluctuations, is poorly understood.
Purpose of the Study:
- To develop a stochastic pharmacokinetic model for chiral drugs accounting for non-adherence in dosing.
- To quantify the impact of medication non-adherence on enantiomeric concentration variability and the discrepancy between active and total drug concentrations.
Main Methods:
- Developed a stochastic pharmacokinetic model incorporating dual stochasticity in dosing intervals and dosages for chiral drugs.
- Utilized characteristic functions and Volterra integral equations to derive expressions for concentration expectation and variance.
- Applied Kesten theorem and ergodic theory to demonstrate the existence and geometric ergodicity of the stationary probability distribution.
- Simulated medication non-adherence scenarios using ibuprofen as a case study.
Main Results:
- Stochastic concentrations significantly deviate from ideal levels under non-adherence.
- Non-adherence induces a non-negligible discrepancy between effective (active moiety) and total measured drug concentrations.
- Quantified enantiomeric randomness in chiral drug concentrations due to medication non-adherence.
Conclusions:
- Provides a rigorous theoretical framework for understanding chiral drug enantiomer variability induced by medication non-adherence.
- Offers insights into enhancing therapeutic efficacy and safety by characterizing concentration fluctuations.
- Highlights the importance of considering non-adherence in chiral drug pharmacokinetic modeling.
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