Population pharmacokinetic model of Vancomycin based on therapeutic drug monitoring data in critically ill septic patients
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2020
Authors
Kovačević, TijanaMiljković, Branislava
Kovačević, Peđa
Dragić, Saša
Momčićević, Danica
Avram, Sanja
Jovanović, Marija
Vučićević, Katarina
Article (Published version)
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Purpose: The present study aimed to establish a population pharmacokinetic model of vancomycin, including adult critically ill septic patients, with normal and impaired renal function.
Materials and methods: A prospective analysis of 146 concentrations from 73 adult critically ill septic patients treated with 1-h intravenous infusion of vancomycin were included in the study. A nonlinear mixed effects modeling (NONMEM) approach was applied for data analysis and evaluation of the final model. The influence of creatinine clearance calculated by the Cockcroft-Gault equation (CrCl), and other potential covariates on vancomycin clearance (CL) were evaluated.
Results: The final one-compartment pharmacokinetic model includes the effect of CrCl on CL. Population pharmacokinetic values for a typical subject were estimated at 0.024 l/h for CL dependent on renal function (CLCrCl), 1.93 l/h for residual portion of CL (not dependent on renal function), and 0.511 l/kg for volume of distribution... (V). According to the final model, for patients with CrCl = 120 ml/min, the median vancomycin total CL is 4.81 l/h, while CrCl-dependent fraction accounts for approximately 60% of CL.
Conclusions: The developed population vancomycin model may be used in estimating individual CL for adult critically ill septic patients, and could be applied for individualizing dosage regimens taking into account the continuous effect of CrCl.
Keywords:
Antibiotics / Creatinine clearance / NONMEM / Renal function / TDMSource:
Journal of Critical Care, 2020, 55, 116-121Publisher:
- Elsevier Inc.
DOI: 10.1016/j.jcrc.2019.10.012
ISSN: 0883-9441
PubMed: 31715528
WoS: 000502604200017
Scopus: 2-s2.0-85074704178
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PharmacyTY - JOUR AU - Kovačević, Tijana AU - Miljković, Branislava AU - Kovačević, Peđa AU - Dragić, Saša AU - Momčićević, Danica AU - Avram, Sanja AU - Jovanović, Marija AU - Vučićević, Katarina PY - 2020 UR - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4826 AB - Purpose: The present study aimed to establish a population pharmacokinetic model of vancomycin, including adult critically ill septic patients, with normal and impaired renal function. Materials and methods: A prospective analysis of 146 concentrations from 73 adult critically ill septic patients treated with 1-h intravenous infusion of vancomycin were included in the study. A nonlinear mixed effects modeling (NONMEM) approach was applied for data analysis and evaluation of the final model. The influence of creatinine clearance calculated by the Cockcroft-Gault equation (CrCl), and other potential covariates on vancomycin clearance (CL) were evaluated. Results: The final one-compartment pharmacokinetic model includes the effect of CrCl on CL. Population pharmacokinetic values for a typical subject were estimated at 0.024 l/h for CL dependent on renal function (CLCrCl), 1.93 l/h for residual portion of CL (not dependent on renal function), and 0.511 l/kg for volume of distribution (V). According to the final model, for patients with CrCl = 120 ml/min, the median vancomycin total CL is 4.81 l/h, while CrCl-dependent fraction accounts for approximately 60% of CL. Conclusions: The developed population vancomycin model may be used in estimating individual CL for adult critically ill septic patients, and could be applied for individualizing dosage regimens taking into account the continuous effect of CrCl. PB - Elsevier Inc. T2 - Journal of Critical Care T1 - Population pharmacokinetic model of Vancomycin based on therapeutic drug monitoring data in critically ill septic patients VL - 55 SP - 116 EP - 121 DO - 10.1016/j.jcrc.2019.10.012 ER -
@article{ author = "Kovačević, Tijana and Miljković, Branislava and Kovačević, Peđa and Dragić, Saša and Momčićević, Danica and Avram, Sanja and Jovanović, Marija and Vučićević, Katarina", year = "2020", abstract = "Purpose: The present study aimed to establish a population pharmacokinetic model of vancomycin, including adult critically ill septic patients, with normal and impaired renal function. Materials and methods: A prospective analysis of 146 concentrations from 73 adult critically ill septic patients treated with 1-h intravenous infusion of vancomycin were included in the study. A nonlinear mixed effects modeling (NONMEM) approach was applied for data analysis and evaluation of the final model. The influence of creatinine clearance calculated by the Cockcroft-Gault equation (CrCl), and other potential covariates on vancomycin clearance (CL) were evaluated. Results: The final one-compartment pharmacokinetic model includes the effect of CrCl on CL. Population pharmacokinetic values for a typical subject were estimated at 0.024 l/h for CL dependent on renal function (CLCrCl), 1.93 l/h for residual portion of CL (not dependent on renal function), and 0.511 l/kg for volume of distribution (V). According to the final model, for patients with CrCl = 120 ml/min, the median vancomycin total CL is 4.81 l/h, while CrCl-dependent fraction accounts for approximately 60% of CL. Conclusions: The developed population vancomycin model may be used in estimating individual CL for adult critically ill septic patients, and could be applied for individualizing dosage regimens taking into account the continuous effect of CrCl.", publisher = "Elsevier Inc.", journal = "Journal of Critical Care", title = "Population pharmacokinetic model of Vancomycin based on therapeutic drug monitoring data in critically ill septic patients", volume = "55", pages = "116-121", doi = "10.1016/j.jcrc.2019.10.012" }
Kovačević, T., Miljković, B., Kovačević, P., Dragić, S., Momčićević, D., Avram, S., Jovanović, M.,& Vučićević, K.. (2020). Population pharmacokinetic model of Vancomycin based on therapeutic drug monitoring data in critically ill septic patients. in Journal of Critical Care Elsevier Inc.., 55, 116-121. https://doi.org/10.1016/j.jcrc.2019.10.012
Kovačević T, Miljković B, Kovačević P, Dragić S, Momčićević D, Avram S, Jovanović M, Vučićević K. Population pharmacokinetic model of Vancomycin based on therapeutic drug monitoring data in critically ill septic patients. in Journal of Critical Care. 2020;55:116-121. doi:10.1016/j.jcrc.2019.10.012 .
Kovačević, Tijana, Miljković, Branislava, Kovačević, Peđa, Dragić, Saša, Momčićević, Danica, Avram, Sanja, Jovanović, Marija, Vučićević, Katarina, "Population pharmacokinetic model of Vancomycin based on therapeutic drug monitoring data in critically ill septic patients" in Journal of Critical Care, 55 (2020):116-121, https://doi.org/10.1016/j.jcrc.2019.10.012 . .