CPhaMAS: An online platform for pharmacokinetic data analysis based on optimized parameter fitting algorithm

Yun Kuang; Dong-Sheng Cao; Yong-Hui Zuo; Jing-Han Yuan; Feng Lu; Yi Zou; Hong Wang; Dan Jiang; Qi Pei; Guo-Ping Yang

doi:10.1016/j.cmpb.2024.108137

CPhaMAS: An online platform for pharmacokinetic data analysis based on optimized parameter fitting algorithm

Comput Methods Programs Biomed. 2024 May:248:108137. doi: 10.1016/j.cmpb.2024.108137. Epub 2024 Mar 19.

Authors

Yun Kuang¹, Dong-Sheng Cao², Yong-Hui Zuo³, Jing-Han Yuan³, Feng Lu³, Yi Zou⁴, Hong Wang⁴, Dan Jiang⁵, Qi Pei⁶, Guo-Ping Yang⁷

Affiliations

¹ Center of Clinical Pharmacology, The Third Xiangya Hospital, Central South University, Changsha, 410013, China; XiangYa School of Pharmaceutical Sciences, Central South University, Changsha, 410083, China.
² XiangYa School of Pharmaceutical Sciences, Central South University, Changsha, 410083, China.
³ Changsha Xutong Technology Co., LTD, Changsha, 410205, China.
⁴ School of Mathematics and Statistics, Central South University, Changsha, China.
⁵ Changsha Xutong Technology Co., LTD, Changsha, 410205, China. Electronic address: 819027527@qq.com.
⁶ Department of pharmacy, the Third Xiangya Hospital, Central South University, Changsha, 410013, China; Furong Laboratory, Changsha, 410013, China. Electronic address: peiqi1028@126.com.
⁷ Center of Clinical Pharmacology, The Third Xiangya Hospital, Central South University, Changsha, 410013, China; XiangYa School of Pharmaceutical Sciences, Central South University, Changsha, 410083, China; Furong Laboratory, Changsha, 410013, China. Electronic address: ygp9880@126.com.

PMID: 38520784
DOI: 10.1016/j.cmpb.2024.108137

Abstract

Background and objective: Clinical pharmacological modeling and statistical analysis software is an essential basic tool for drug development and personalized drug therapy. The learning curve of current basic tools is steep and unfriendly to beginners. The curve is even more challenging in cases of significant individual differences or measurement errors in data, resulting in difficulties in accurately estimating pharmacokinetic parameters by existing fitting algorithms. Hence, this study aims to explore a new optimized parameter fitting algorithm that reduces the sensitivity of the model to initial values and integrate it into the CPhaMAS platform, a user-friendly online application for pharmacokinetic data analysis.

Methods: In this study, we proposed an optimized Nelder-Mead method that reinitializes simplex vertices when trapped in local solutions and integrated it into the CPhaMAS platform. The CPhaMAS, an online platform for pharmacokinetic data analysis, includes three modules: compartment model analysis, non-compartment analysis (NCA) and bioequivalence/bioavailability (BE/BA) analysis. Our proposed CPhaMAS platform was evaluated and compared with existing WinNonlin.

Results: The platform was easy to learn and did not require code programming. The accuracy investigation found that the optimized Nelder-Mead method of the CPhaMAS platform showed better accuracy (smaller mean relative error and higher R²) in two-compartment and extravascular administration models when the initial value was set to true and abnormal values (10 times larger or smaller than the true value) compared with the WinNonlin. The mean relative error of the NCA calculation parameters of CPhaMAS and WinNonlin was <0.0001 %. When calculating BE for conventional, high-variability and narrow-therapeutic drugs. The main statistical parameters of the parameters C_max, AUC_t, and AUC_inf in CPhaMAS have a mean relative error of <0.01% compared to WinNonLin.

Conclusions: In summary, CPhaMAS is a user-friendly platform with relatively accurate algorithms. It is a powerful tool for analysing pharmacokinetic data for new drug development and precision medicine.

Keywords: CPhaMAS; Online platform; Optimized Nelder-Mead method; Pharmacokinetic data analysis.

MeSH terms

Algorithms*
Models, Theoretical
Pharmaceutical Preparations
Research Design
Software*

Substances

Pharmaceutical Preparations