Statistical Analysis of Two-Compartment Pharmacokinetic Models with Drug Non-adherence.

Bull Math Biol

School of Mathematics and Statistics, Shaanxi Normal University, Xi'an, 710119, People's Republic of China.

Published: June 2023

Poor drug adherence is considered one of major barriers to achieving the clinical and public health benefits of many pharmacotherapies. In the current paper, we aim to investigate the impact of dose omission on the plasma concentrations of two-compartment pharmacokinetic models with two typical routes of drug administration, namely the intravenous bolus and extravascular first-order absorption. First, we reformulate the classical two-compartment pharmacokinetic models with a new stochastic feature, where a binomial random model of dose intake is integrated. Then, we formalize the explicit expressions of expectation and variance for trough concentrations and limit concentrations, with the latter proved of the existence and uniqueness for steady-state distribution. Moreover, we mathematically demonstrate the strict stationarity and ergodicity of trough concentrations as a Markov chain. In addition, we numerically simulate the impact of drug non-adherence to different extents on the variability and regularity of drug concentration and compare the drug pharmacokinetic preference between one and two compartment pharmacokinetic models. The results of sensitivity analysis also suggest the drug non-adherence as one of the most sensitive model parameters to the expectation of limit concentration. Our modelling and analytical approach can be integrated into the chronic disease models to estimate or quantitatively predict the therapy efficacy with drug pharmacokinetics presumably affected by random dose omissions.

Download full-text PDF

Source
http://dx.doi.org/10.1007/s11538-023-01173-0DOI Listing

Publication Analysis

Top Keywords

pharmacokinetic models
16
two-compartment pharmacokinetic
12
drug non-adherence
12
drug
8
trough concentrations
8
pharmacokinetic
5
models
5
statistical analysis
4
analysis two-compartment
4
models drug
4

Similar Publications

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!