Development of a Web Application for Simulating Plasma Drug Concentrations in Patients with Zolpidem Intoxication

Author:

Cha Hwa Jun12ORCID,Han Sungpil12ORCID,Pak Kwan Cheol3,Kim Hyungsub4

Affiliation:

1. Department of Pharmacology, College of Medicine, The Catholic University of Korea, Seoul 06591, Republic of Korea

2. PIPET (Pharmacometrics Institute for Practical Education and Training), College of Medicine, The Catholic University of Korea, Seoul 06591, Republic of Korea

3. Yuhan Corporation, Seoul 06927, Republic of Korea

4. Department of Paramedicine, College of Health Sciences, Eulji University, Seongnam 13135, Republic of Korea

Abstract

Zolpidem is a widely prescribed hypnotic Z-drug used to treat short-term insomnia. However, a growing number of individuals intentionally overdose on these drugs. This study aimed to develop a predictive tool for physicians to assess patients with zolpidem overdose. A population pharmacokinetic (PK) model was established using digitized data obtained from twenty-three healthy volunteers after a single oral administration of zolpidem. Based on the final PK model, a web application was developed using open-source R packages such as rxode2, nonmem2rx, and shiny. The final model was a one-compartment model with first-order absorption and elimination with PK parameters, including clearance (CL, 16.9 L/h), absorption rate constant (Ka, 5.41 h−1), volume of distribution (Vd, 61.7 L), and lag time (ALAG, 0.394 h). Using the established population PK model in the current study, we developed a web application that enables users to simulate plasma zolpidem concentrations and visualize their profiles. This user-friendly web application may provide essential clinical information to physicians, ultimately helping in the management of patients with zolpidem intoxication.

Funder

Eulji University

Publisher

MDPI AG

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