Population Pharmacokinetic Analysis Proves Superiority of
Continuous Infusion in PK/PD Target Attainment with Oxacillin
in Staphylococcal Infections

J 2022

Population Pharmacokinetic Analysis Proves Superiority of Continuous Infusion in PK/PD Target Attainment with Oxacillin in Staphylococcal Infections

MURÍNOVÁ, Irena, Martin SVIDRNOCH, Tomas GUCKY, Jan HLAVAC, Pavel MICHALEK et. al.

Basic information

Original name

Population Pharmacokinetic Analysis Proves Superiority of Continuous Infusion in PK/PD Target Attainment with Oxacillin in Staphylococcal Infections

Authors

MURÍNOVÁ, Irena (203 Czech Republic, belonging to the institution), Martin SVIDRNOCH, Tomas GUCKY, Jan HLAVAC, Pavel MICHALEK, Ondrej SLANAR and Martin SIMA (guarantor)

Edition

Antibiotics, BASEL, MDPI, 2022, 2079-6382

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

30104 Pharmacology and pharmacy

Country of publisher

Switzerland

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

URL

Impact factor

Impact factor: 4.800

RIV identification code

RIV/00216224:14160/22:00128006

Organization unit

Faculty of Pharmacy

DOI

http://dx.doi.org/10.3390/antibiotics11121736

UT WoS

000900615800001

Keywords in English

antibiotics; nonlinear mixed-effects modeling; glomerular filtration rate; dosing regimen; oxacillin; Monte Carlo simulations

Abstract

V originále

Considering its very short elimination half-life, the approved oxacillin dosage might not be sufficient to maintain the pharmacokinetic/pharmacodynamics (PK/PD) target of time-dependent antibiotics. This study aimed to describe the population pharmacokinetics of oxacillin and to explore the probability of PK/PD target attainment by using various dosing regimens with oxacillin in staphylococcal infections. Both total and unbound oxacillin plasma concentrations retrieved as a part of routine therapeutic drug-monitoring practice were analyzed using nonlinear mixed-effects modeling. Monte Carlo simulations were used to generate the theoretical distribution of unbound oxacillin plasma concentration-time profiles at various dosage regimens. Data from 24 patients treated with oxacillin for staphylococcal infection have been included into the analysis. The volume of distribution of oxacillin in the population was 11.2 L, while the elimination rate constant baseline of 0.73 h(-1) increased by 0.3 h(-1) with each 1 mL/s/1.73 m(2) of the estimated glomerular filtration rate (eGFR). The median value of oxacillin binding to plasma proteins was 86%. The superiority of continuous infusion in achieving target PK/PD values was demonstrated and dosing according to eGFR was proposed. Daily oxacillin doses of 9.5 g, 11 g, or 12.5 g administered by continuous infusion have been shown to be optimal for achieving target PK/PD values in patients with moderate, mild, or normal renal function, respectively.

Citovat

MURÍNOVÁ, Irena, Martin SVIDRNOCH, Tomas GUCKY, Jan HLAVAC, Pavel MICHALEK, Ondrej SLANAR and Martin SIMA. Population Pharmacokinetic Analysis Proves Superiority of Continuous Infusion in PK/PD Target Attainment with Oxacillin in Staphylococcal Infections. Antibiotics. BASEL: MDPI, 2022, vol. 11, No 12, p. 1-11. ISSN 2079-6382. Available from: https://dx.doi.org/10.3390/antibiotics11121736.

@article{2246993,
   author = {Murínová, Irena and Svidrnoch, Martin and Gucky, Tomas and Hlavac, Jan and Michalek, Pavel and Slanar, Ondrej and Sima, Martin},
   article_location = {BASEL},
   article_number = {12},
   doi = {http://dx.doi.org/10.3390/antibiotics11121736},
   keywords = {antibiotics; nonlinear mixed-effects modeling; glomerular filtration rate; dosing regimen; oxacillin; Monte Carlo simulations},
   language = {eng},
   issn = {2079-6382},
   journal = {Antibiotics},
   title = {Population Pharmacokinetic Analysis Proves Superiority of Continuous Infusion in PK/PD Target Attainment with Oxacillin in Staphylococcal Infections},
   url = {https://www.mdpi.com/2079-6382/11/12/1736},
   volume = {11},
   year = {2022}
}

TY  - JOUR
ID  - 2246993
AU  - Murínová, Irena - Svidrnoch, Martin - Gucky, Tomas - Hlavac, Jan - Michalek, Pavel - Slanar, Ondrej - Sima, Martin
PY  - 2022
TI  - Population Pharmacokinetic Analysis Proves Superiority of Continuous Infusion in PK/PD Target Attainment with Oxacillin in Staphylococcal Infections
JF  - Antibiotics
VL  - 11
IS  - 12
SP  - 1-11
EP  - 1-11
PB  - MDPI
SN  - 20796382
KW  - antibiotics
KW  - nonlinear mixed-effects modeling
KW  - glomerular filtration rate
KW  - dosing regimen
KW  - oxacillin
KW  - Monte Carlo simulations
UR  - https://www.mdpi.com/2079-6382/11/12/1736
N2  - Considering its very short elimination half-life, the approved oxacillin dosage might not be sufficient to maintain the pharmacokinetic/pharmacodynamics (PK/PD) target of time-dependent antibiotics. This study aimed to describe the population pharmacokinetics of oxacillin and to explore the probability of PK/PD target attainment by using various dosing regimens with oxacillin in staphylococcal infections. Both total and unbound oxacillin plasma concentrations retrieved as a part of routine therapeutic drug-monitoring practice were analyzed using nonlinear mixed-effects modeling. Monte Carlo simulations were used to generate the theoretical distribution of unbound oxacillin plasma concentration-time profiles at various dosage regimens. Data from 24 patients treated with oxacillin for staphylococcal infection have been included into the analysis. The volume of distribution of oxacillin in the population was 11.2 L, while the elimination rate constant baseline of 0.73 h(-1) increased by 0.3 h(-1) with each 1 mL/s/1.73 m(2) of the estimated glomerular filtration rate (eGFR). The median value of oxacillin binding to plasma proteins was 86%. The superiority of continuous infusion in achieving target PK/PD values was demonstrated and dosing according to eGFR was proposed. Daily oxacillin doses of 9.5 g, 11 g, or 12.5 g administered by continuous infusion have been shown to be optimal for achieving target PK/PD values in patients with moderate, mild, or normal renal function, respectively.
ER  -

MURÍNOVÁ, Irena, Martin SVIDRNOCH, Tomas GUCKY, Jan HLAVAC, Pavel MICHALEK, Ondrej SLANAR and Martin SIMA. Population Pharmacokinetic Analysis Proves Superiority of Continuous Infusion in PK/PD Target Attainment with Oxacillin in Staphylococcal Infections. \textit{Antibiotics}. BASEL: MDPI, 2022, vol.~11, No~12, p.~1-11. ISSN~2079-6382. Available from: https://dx.doi.org/10.3390/antibiotics11121736.

Detailed Information on Publication Record