Development of a Web Application for Simulating Plasma Drug Concentrations in Patients with Zolpidem Intoxication
Abstract
1. Introduction
2. Materials and Methods
2.1. Study Design and Data
2.2. Population PK Model
2.3. Model Evaluation
2.4. RxODE Conversion and Simulation
2.5. Development of A Web-Application
3. Results
3.1. Pharmacokinetic Analysis
3.2. Population PK Model
3.3. RxODE Conversion and Simulation
3.4. Zolpidemsim: Web Application
3.5. Simulation Results at Various Doses
4. Discussion
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Parameters | Male | Female | ||
---|---|---|---|---|
Original (N = 15) | Digitized (N = 12) | Original (N = 15) | Digitized (N = 11) | |
Cmax (ng/mL) | 161.21 (46.74) | 162.72 (47.04) | 187.64 (59.44) | 189.22 (59.85) |
AUC0–12h (ng h/mL) | 537.9 (202.3) | 542.5 (197.5) | 696.9 (221.7) | 688.1 (221.3) |
CL/F (L/h) | 19.76 (7.25) | 18.88 (6.06) | 14.72 (4.07) | 14.93 (4.22) |
Lambda z (1/h) | 0.27 (0.09) | 0.22 (0.06) | 0.23 (0.03) | 0.24 (0.04) |
Half-life (h) | 2.93 (1.14) | 3.58 (1.10) | 3.05 (0.35) | 3.02 (0.52) |
Vd/F (L) | 74.8 (16.2) | 92.2 (35.7) | 63.6 (15.6) | 63.5 (16.5) |
Tmax (h) | 0.94 (0.58–1.80) | 0.96 (0.58–1.78) | 0.83 (0.58–3.33) | 0.84 (0.57–3.36) |
Parameters | Estimates (RSE a %) | Bootstrap | |
---|---|---|---|
Median | 95% CI | ||
Fixed effects | |||
Ka (1/h) | 5.41 (45.47) | 5.66 | 3.24–11.24 |
Vd/F (L) | 61.70 (5.82) | 61.33 | 54.89–68.64 |
CL/F (L/h) | 16.90 (8.40) | 16.87 | 14.29–19.50 |
ALAG (h) | 0.394 (6.24) | 0.394 | 0.385–0.493 |
Interindividual variability (IIV) | |||
ω2 Ka (CV b %) | 158.91 (43.65) | 157.81 | 69.76–444.98 |
ω2 Vd (CV%) | 22.10 (47.17) | 20.98 | 12.0–29.68 |
ω2 CL (CV%) | 32.60 (45.54) | 31.74 | 20.96–41.65 |
ρVd-CL | 0.853 | 0.853 | 0.796–0.869 |
Residual variability | |||
Proportional error | 0.284 (6.16) | 0.283 | 0.242–0.319 |
Doses (mg) | NR a (%) | <1 h (%) | 1–2 h (%) | 2–3 h (%) | >3 h (%) | |
---|---|---|---|---|---|---|
Toxic concentration (500–1500 ng/mL) | 10 | 100 | 0 | 0 | 0 | 0 |
280 | 0 | 0 | 0 | 0 | 100 | |
560 | 0 | 0 | 0 | 0 | 100 | |
1120 | 0 | 0 | 0 | 0 | 100 | |
Comatose concentration (1500–4000 ng/mL) | 10 | 100 | 0 | 0 | 0 | 0 |
280 | 0.2 | 0.4 | 0.8 | 15.0 | 83.6 | |
560 | 0 | 0 | 0 | 0.4 | 99.6 | |
1120 | 0 | 0 | 0 | 0 | 100 | |
Fatal concentration (>4000 ng/mL) | 10 | 100 | 0 | 0 | 0 | 0 |
280 | 58.8 | 21.4 | 15.6 | 4.0 | 0.2 | |
560 | 2.6 | 1.6 | 11.2 | 31.4 | 53.2 | |
1120 | 0 | 0 | 0 | 1.6 | 98.4 |
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Cha, H.J.; Han, S.; Pak, K.C.; Kim, H. Development of a Web Application for Simulating Plasma Drug Concentrations in Patients with Zolpidem Intoxication. Pharmaceutics 2024, 16, 689. https://doi.org/10.3390/pharmaceutics16050689
Cha HJ, Han S, Pak KC, Kim H. Development of a Web Application for Simulating Plasma Drug Concentrations in Patients with Zolpidem Intoxication. Pharmaceutics. 2024; 16(5):689. https://doi.org/10.3390/pharmaceutics16050689
Chicago/Turabian StyleCha, Hwa Jun, Sungpil Han, Kwan Cheol Pak, and Hyungsub Kim. 2024. "Development of a Web Application for Simulating Plasma Drug Concentrations in Patients with Zolpidem Intoxication" Pharmaceutics 16, no. 5: 689. https://doi.org/10.3390/pharmaceutics16050689
APA StyleCha, H. J., Han, S., Pak, K. C., & Kim, H. (2024). Development of a Web Application for Simulating Plasma Drug Concentrations in Patients with Zolpidem Intoxication. Pharmaceutics, 16(5), 689. https://doi.org/10.3390/pharmaceutics16050689