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@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.
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