Intracellular PD Modelling (PDi) for the Prediction of Clinical Activity of Increased Rifampicin Dosing
Abstract
1. Introduction
2. Materials and Methods
2.1. PDi Modelling
2.2. Hazard Ratio Calculation
2.3. PK Monte Carlo Simulations
3. Results
3.1. PDi Modelling Predicts Efficacy of Standard and High-Dose RIF-Containing Treatments
3.2. PDi Modelling Suggests No Further Reduction in Time to Culture Conversion Rates by Increasing RIF Dose Beyond 35 mg/kg
3.3. PDi Modelling Predicts a Dose-Effect Relationship of RIF
3.4. PK Simulation Analysis
4. Discussion
Supplementary Materials
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Boeree et al. (2017) [14] (Observed) | PDi Prediction | ||||
---|---|---|---|---|---|
Standard HRZE | H35RZE | Standard HRZE | H35RZE | H70RZE | |
Total in Analysis | 123 | 63 | 123 | 63 | 63 |
Hazard ratio over 8 weeks (CI) * | N/A | 1.73 (1.07–2.82), p = 0.004 (unadjusted) | |||
N/A | 2.06 (1.26–3.38), p = 0.004 (adjusted) | N/A | 2.04 (1.41–2.94), p < 0.001 | 2.16 (1.50–3.12), p < 0.001 | |
Hazard ratio over 12 weeks (CI) | N/A | 1.46 (1.02–2.11), p = 0.04 (unadjusted) | |||
N/A | 1.78 (1.22–2.58), p = 0.003 (adjusted) | N/A | 1.68 (1.21–2.32), p < 0.001 | 1.86 (1.35–2.57), p < 0.001 | |
No. of culture conversions during 26-weeks (MGIT **) (% of patients) | 101 (82%) | 51 (81%) | 104 (94%) | 62 (99%) | 63 (100%) |
Median time to culture conversion (IQR) *** | 62 (4–83) | 48 (34–69) | 55 (41–76) | 40 (34–51) | 39 (32–48) |
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Aljayyoussi, G.; Donnellan, S.; Ward, S.A.; Biagini, G.A. Intracellular PD Modelling (PDi) for the Prediction of Clinical Activity of Increased Rifampicin Dosing. Pharmaceutics 2019, 11, 278. https://doi.org/10.3390/pharmaceutics11060278
Aljayyoussi G, Donnellan S, Ward SA, Biagini GA. Intracellular PD Modelling (PDi) for the Prediction of Clinical Activity of Increased Rifampicin Dosing. Pharmaceutics. 2019; 11(6):278. https://doi.org/10.3390/pharmaceutics11060278
Chicago/Turabian StyleAljayyoussi, Ghaith, Samantha Donnellan, Stephen A. Ward, and Giancarlo A. Biagini. 2019. "Intracellular PD Modelling (PDi) for the Prediction of Clinical Activity of Increased Rifampicin Dosing" Pharmaceutics 11, no. 6: 278. https://doi.org/10.3390/pharmaceutics11060278
APA StyleAljayyoussi, G., Donnellan, S., Ward, S. A., & Biagini, G. A. (2019). Intracellular PD Modelling (PDi) for the Prediction of Clinical Activity of Increased Rifampicin Dosing. Pharmaceutics, 11(6), 278. https://doi.org/10.3390/pharmaceutics11060278