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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.

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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  -

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
Original language	English
Type of outcome	Article in a journal
Field of Study	30104 Pharmacology and pharmacy
Country of publisher	Switzerland
Confidentiality degree	is not subject to a state or trade secret
WWW	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
Tags	rivok, ÚAF
Tags	International impact, Reviewed
Changed by	Changed by: JUDr. Sabina Krejčiříková, učo 383857. Changed: 16/1/2023 09:34.

Abstract
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.

Abstract

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.