Imipenem/Relebactam Ex Vivo Clearance during Continuous Renal Replacement Therapy
Abstract
:1. Introduction
2. Results
3. Discussion
4. Materials and Methods
4.1. Degradation
4.2. Adsorption
4.3. Continuous Hemofiltration
4.4. Continuous Hemodialysis
4.5. Sample Analysis
4.6. Monte Carlo Dosing Simulations
4.7. Pharmacodynamic Targets
4.8. Optimal Dosing Regimen
4.9. Data Analysis
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Effluent Rate (mL/min) | HF1400 (n = 6, Mean ± SD) | M150 (n = 6, Mean ± SD) | ||
---|---|---|---|---|
Imipenem | Relebactam | Imipenem | Relebactam | |
Sieving coefficients | ||||
16.7 | 1.06 ± 0.2 | 0.95 ± 0.08 * | 1.19 ± 0.2 | 1.07 ± 0.06 * |
33.3 | 1.1 ± 0.2 | 1.00 ± 0.04 * | 1.1 ± 0.2 | 1.08 ± 0.1 * |
50 | 1.01 ± 0.2 | 0.94 ± 0.08 | 1.3 ± 0.2 | 1.12 ± 0.06 |
Saturation coefficients | ||||
16.7 | 1.2 ± 0.3 | 1.2 ± 0.06 * | 0.9 ± 0.4 | 0.9 ± 0.2 * |
33.3 | 1.7 ± 1.3 | 1 ± 0.2 | 0.99 ± 0.5 | 0.9 ± 0.5 |
50 | 1.2 ± 0.3 | 1.1 ± 0.1 | 1.23 ± 0.1 | 1.1 ± 0.1 |
100 | 1.1 ± 0.2 | 1.02 ± 0.1 * | 1.17 ± 0.2 | 0.9 ± 0.05 * |
Pharmacokinetic Parameters | Imipenem [12] | Relebactam [13,14] |
---|---|---|
Vd (L/kg) | 0.34 ± 0.1 (0.21−0.63) | 0.19 ± 0.11 (0.08−0.53) |
Free Fraction | 0.8 ± 0.16 (0−1) | 0.78 ± 0.2 (0−1) |
NR CL (mL/min) | 100.5 ± 28 (53−160) | 11.7 ± 3.3 (11.2−12.2) |
Sieving coefficient | 1 ± 0.2 (0−1) | 1 ± 0.04 (0−1) |
r2 weight & Vd | 0.17 | N/A |
r2 weight & NR CL | 0.013 | N/A |
Weight ± SD (kg) | ) [15] |
Antimicrobial Dosing | 40% fT > 1 × MIC | 40% fT > 4 × MIC | 100%fT > MIC |
---|---|---|---|
Imipenem | |||
200 mg q6h | 100% | 0% | 0% |
300 mg q6h | 100% | 2% | 0% |
400 mg q6h | 100% | 28.6% | 33.5% |
500 mg q6h | 100% | 66.1% | 60% |
600 mg q6h | 100% | 90.8% | 77.2% |
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Jang, S.M.; Yessayan, L.; Dean, M.; Costello, G.; Katwaru, R.; Mueller, B.A. Imipenem/Relebactam Ex Vivo Clearance during Continuous Renal Replacement Therapy. Antibiotics 2021, 10, 1184. https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics10101184
Jang SM, Yessayan L, Dean M, Costello G, Katwaru R, Mueller BA. Imipenem/Relebactam Ex Vivo Clearance during Continuous Renal Replacement Therapy. Antibiotics. 2021; 10(10):1184. https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics10101184
Chicago/Turabian StyleJang, Soo Min, Lenar Yessayan, Michael Dean, Gabrielle Costello, Ravi Katwaru, and Bruce A. Mueller. 2021. "Imipenem/Relebactam Ex Vivo Clearance during Continuous Renal Replacement Therapy" Antibiotics 10, no. 10: 1184. https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics10101184