Population Pharmacokinetic Analysis Proves Superiority of Continuous Infusion in PK/PD Target Attainment with Oxacillin in Staphylococcal Infections
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 probabil...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-12-01
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| Series: | Antibiotics |
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| Online Access: | https://www.mdpi.com/2079-6382/11/12/1736 |
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| author | Irena Murínová Martin Švidrnoch Tomáš Gucký Jan Hlaváč Pavel Michálek Ondřej Slanař Martin Šíma |
| author_facet | Irena Murínová Martin Švidrnoch Tomáš Gucký Jan Hlaváč Pavel Michálek Ondřej Slanař Martin Šíma |
| author_sort | Irena Murínová |
| collection | DOAJ |
| description | 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<sup>−1</sup> increased by 0.3 h<sup>−1</sup> with each 1 mL/s/1.73 m<sup>2</sup> 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. |
| first_indexed | 2024-03-09T17:24:14Z |
| format | Article |
| id | doaj.art-a4c85c7bcfd94b38ac8b39528f417662 |
| institution | Directory Open Access Journal |
| issn | 2079-6382 |
| language | English |
| last_indexed | 2024-03-09T17:24:14Z |
| publishDate | 2022-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Antibiotics |
| spelling | doaj.art-a4c85c7bcfd94b38ac8b39528f4176622023-11-24T12:53:29ZengMDPI AGAntibiotics2079-63822022-12-011112173610.3390/antibiotics11121736Population Pharmacokinetic Analysis Proves Superiority of Continuous Infusion in PK/PD Target Attainment with Oxacillin in Staphylococcal InfectionsIrena Murínová0Martin Švidrnoch1Tomáš Gucký2Jan Hlaváč3Pavel Michálek4Ondřej Slanař5Martin Šíma6Department of Clinical Pharmacy, Military University Hospital Prague, 16902 Prague, Czech RepublicLaboratory of Pharmacology and Toxicology, AGEL Laboratories, 74101 Novy Jicin, Czech RepublicLaboratory of Pharmacology and Toxicology, AGEL Laboratories, 74101 Novy Jicin, Czech RepublicDepartment of Pharmacology, First Faculty of Medicine, Charles University and General University Hospital in Prague, 12800 Prague, Czech RepublicDepartment of Anaesthesia and Intensive Care, First Faculty of Medicine, Charles University and General University Hospital in Prague, 12808 Prague, Czech RepublicDepartment of Pharmacology, First Faculty of Medicine, Charles University and General University Hospital in Prague, 12800 Prague, Czech RepublicDepartment of Pharmacology, First Faculty of Medicine, Charles University and General University Hospital in Prague, 12800 Prague, Czech RepublicConsidering 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<sup>−1</sup> increased by 0.3 h<sup>−1</sup> with each 1 mL/s/1.73 m<sup>2</sup> 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.https://www.mdpi.com/2079-6382/11/12/1736antibioticsnonlinear mixed-effects modelingglomerular filtration ratedosing regimenoxacillinMonte Carlo simulations |
| spellingShingle | Irena Murínová Martin Švidrnoch Tomáš Gucký Jan Hlaváč Pavel Michálek Ondřej Slanař Martin Šíma Population Pharmacokinetic Analysis Proves Superiority of Continuous Infusion in PK/PD Target Attainment with Oxacillin in Staphylococcal Infections Antibiotics antibiotics nonlinear mixed-effects modeling glomerular filtration rate dosing regimen oxacillin Monte Carlo simulations |
| title | Population Pharmacokinetic Analysis Proves Superiority of Continuous Infusion in PK/PD Target Attainment with Oxacillin in Staphylococcal Infections |
| title_full | Population Pharmacokinetic Analysis Proves Superiority of Continuous Infusion in PK/PD Target Attainment with Oxacillin in Staphylococcal Infections |
| title_fullStr | Population Pharmacokinetic Analysis Proves Superiority of Continuous Infusion in PK/PD Target Attainment with Oxacillin in Staphylococcal Infections |
| title_full_unstemmed | Population Pharmacokinetic Analysis Proves Superiority of Continuous Infusion in PK/PD Target Attainment with Oxacillin in Staphylococcal Infections |
| title_short | Population Pharmacokinetic Analysis Proves Superiority of Continuous Infusion in PK/PD Target Attainment with Oxacillin in Staphylococcal Infections |
| title_sort | population pharmacokinetic analysis proves superiority of continuous infusion in pk pd target attainment with oxacillin in staphylococcal infections |
| topic | antibiotics nonlinear mixed-effects modeling glomerular filtration rate dosing regimen oxacillin Monte Carlo simulations |
| url | https://www.mdpi.com/2079-6382/11/12/1736 |
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