Population Pharmacokinetics of Orally Administered Clindamycin to Treat Prosthetic Joint Infections: A Prospective Study
Abstract
:1. Introduction
2. Results
2.1. Patients
2.2. PK Parameters
2.3. Dosing-Regimen Evaluation
3. Discussion
4. Materials and Methods
4.1. Ethics
4.2. Patients
4.3. Treatment
4.4. PK Sampling
4.5. Analytical Methods
4.6. PK Models
4.7. Covariates
4.8. Model Evaluation
4.9. Dosing-Regimen Simulations
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Characteristic | Value |
---|---|
Males/females, n | 13/7 |
Body weight (kg) | 76.3 (14.4) |
Age (years) | 66.5 (15.9) |
Prothrombin time (%) | 85.7 (12.9) |
Total proteins (g/L) | 72.8 (6.15) |
Albumin (g/L) | 37.6 (5.11) |
Aspartate aminotransferase (IU/L) | 16.0 (4.41) |
Alanine aminotransferase (IU/L) | 14.6 (6.10) |
Bilirubin (µmol/L) | 6.83 (3.49) |
Creatinine (µmol/L) | 73.6 (17.2) |
C-reactive protein (mg/L) | 47.6 (79.1) |
Leucocytes (G/L) | 8.19 (3.55) |
Infection localization, n | |
Shoulder arthroplasty | 3 |
Hip arthroplasty | 14 |
Knee arthroplasty | 3 |
Original Dataset | Bootstrap | |||
---|---|---|---|---|
Parameter | Estimate | RSE | Estimate | RSE |
Structural model | ||||
CL/F (L/h) | 23.00 | 8.7% | 23.05 | 9.2% |
V/F (L) | 103.00 | 8.0% | 102.1 | 7.6% |
Ka (/h) | 3.53 | 22.4% | 3.71 | 29.6% |
Interindividual variability | ||||
ω2 CL/F | 0.14 | 24.7% | 0.136 | 25.9% |
ω2 V/F | 0.08 | 28.2% | 0.078 | 28.9% |
ω2 Ka | 0.60 | 46.3% | 0.63 | 66% |
Residual error | ||||
Proportional error Additive error | 0.00976 0.0801 | 36.0% 49.0% | 0.009240 0.0827 | 34.4% 43.2% |
Dosing Regimen | 450 Mg q6h | 600 Mg q8h | 600 Mg q6h | 750 Mg q8h | 750 Mg q6h | 900 Mg q8h | 900 Mg q6h |
---|---|---|---|---|---|---|---|
Median 90% CI | 1.73 0.42–4.10 | 1.31 0.21–4.67 | 2.10 0.41–5.51 | 1.51 0.19–4.92 | 2.81 0.63–6.73 | 1.92 0.31–5.89 | 3.38 0.71–8.55 |
Probability of reaching Ctrough ≥ 2 × MIC | |||||||
MIC = 0.5 mg/L | 75% | 64% | 81% | 70% | 89% | 76% | 92% |
MIC = 0.25 mg/L | 93% | 86% | 94% | 85% | 97% | 91% | 98% |
MIC = 0.125 mg/L | 97% | 93% | 97% | 93% | 99% | 97% | 99% |
MIC = 0.0625 mg/L | 99% | 97% | 99% | 97% | 100% | 99% | 100% |
MIC = 0.03125 mg/L | 100% | 99% | 100% | 98% | 100% | 99% | 100% |
Global PTA for Staphylococcus | 98% | 95% | 98% | 95% | 100% | 98% | 100% |
Global PTA for Streptococcus | 98% | 96% | 99% | 95% | 99% | 98% | 100% |
Probability of reaching Ctrough ≥ 8 × MIC | |||||||
MIC = 0.5 mg/L | 6% | 8% | 16% | 9% | 29% | 15% | 38% |
MIC = 0.25 mg/L | 39% | 30% | 53% | 37% | 68% | 48% | 74% |
MIC = 0.125 mg/L | 75% | 64% | 81% | 70% | 89% | 76% | 92% |
MIC = 0.0625 mg/L | 93% | 86% | 94% | 85% | 97% | 91% | 98% |
MIC = 0.03125 mg/L | 97% | 93% | 97% | 93% | 99% | 97% | 99% |
Global PTA for Staphylococcus | 82% | 73% | 86% | 76% | 92% | 82% | 95% |
Global PTA for Streptococcus | 87% | 79% | 90% | 80% | 94% | 86% | 96% |
Probability to reach the upper limit concentration | |||||||
>5 mg/L | 2% | 3% | 8% | 5% | 18% | 9% | 25% |
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Mimram, L.; Magréault, S.; Kerroumi, Y.; Salmon, D.; Kably, B.; Marmor, S.; Jannot, A.-S.; Jullien, V.; Zeller, V. Population Pharmacokinetics of Orally Administered Clindamycin to Treat Prosthetic Joint Infections: A Prospective Study. Antibiotics 2022, 11, 1462. https://doi.org/10.3390/antibiotics11111462
Mimram L, Magréault S, Kerroumi Y, Salmon D, Kably B, Marmor S, Jannot A-S, Jullien V, Zeller V. Population Pharmacokinetics of Orally Administered Clindamycin to Treat Prosthetic Joint Infections: A Prospective Study. Antibiotics. 2022; 11(11):1462. https://doi.org/10.3390/antibiotics11111462
Chicago/Turabian StyleMimram, Léo, Sophie Magréault, Younes Kerroumi, Dominique Salmon, Benjamin Kably, Simon Marmor, Anne-Sophie Jannot, Vincent Jullien, and Valérie Zeller. 2022. "Population Pharmacokinetics of Orally Administered Clindamycin to Treat Prosthetic Joint Infections: A Prospective Study" Antibiotics 11, no. 11: 1462. https://doi.org/10.3390/antibiotics11111462