Population Pharmacokinetics and Pharmacodynamics of Sitafloxacin in Plasma and Alveolar Epithelial Lining Fluid of Critically Ill Thai Patients With Pneumonia
ABSTRACT Sitafloxacin is one of the oral respiratory quinolones for the treatment of community‐acquired pneumonia. The pharmacokinetic (PK) changes of sitafloxacin in critical illness have been previously reported. However, sitafloxacin exposure and target attainment have never been confirmed in thi...
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2025-04-01
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| Online Access: | https://doi.org/10.1002/prp2.70081 |
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| author | Taniya Paiboonvong Preecha Montakantikul Navarat Panjasawatwong Noppaket Singkham Baralee Punyawudho |
| author_facet | Taniya Paiboonvong Preecha Montakantikul Navarat Panjasawatwong Noppaket Singkham Baralee Punyawudho |
| author_sort | Taniya Paiboonvong |
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| description | ABSTRACT Sitafloxacin is one of the oral respiratory quinolones for the treatment of community‐acquired pneumonia. The pharmacokinetic (PK) changes of sitafloxacin in critical illness have been previously reported. However, sitafloxacin exposure and target attainment have never been confirmed in this population. To develop a population pharmacokinetic (PK) model of sitafloxacin, plasma and epithelial lining fluid (ELF) concentrations were obtained after sitafloxacin administration as a 200‐mg single dose under fasting condition in 12 subjects. A population pharmacokinetic analysis was performed using a nonlinear mixed‐effects modeling approach. The probability of target attainment (PTA) and cumulative fraction of response (CFR) against the MIC distribution of S. pneumoniae isolated from Thai patients was estimated by Monte Carlo simulations. The pharmacokinetics of sitafloxacin in plasma was best described by a one‐compartment model linking to the ELF compartment. The partition coefficient which relates drug exposure in ELF to drug exposure in plasma was estimated to be 0.77. Age was a significant covariate that impacted the relative bioavailability. Results from Monte Carlo simulations showed that the maximum approved dose of sitafloxacin 100 mg q 12 h provided > 90% PTA and CFR in both plasma and ELF. The current maximal dosing of sitafloxacin provided adequate exposure in plasma and ELF for the treatment of critically ill Thai patients with pneumonia. |
| format | Article |
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| institution | OA Journals |
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| language | English |
| publishDate | 2025-04-01 |
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| spelling | doaj-art-19629c19ea624f5cb1f47472debf95fe2025-08-20T02:26:24ZengWileyPharmacology Research & Perspectives2052-17072025-04-01132n/an/a10.1002/prp2.70081Population Pharmacokinetics and Pharmacodynamics of Sitafloxacin in Plasma and Alveolar Epithelial Lining Fluid of Critically Ill Thai Patients With PneumoniaTaniya Paiboonvong0Preecha Montakantikul1Navarat Panjasawatwong2Noppaket Singkham3Baralee Punyawudho4Department of Pharmacy Practice College of Pharmacy, Rangsit University Pathum Thani ThailandDepartment of Pharmacy Faculty of Pharmacy, Mahidol University Bangkok ThailandDepartment of Pharmaceutical Care Faculty of Pharmacy, Payap University Chiang Mai ThailandDivision of Clinical Pharmacy, Department of Pharmaceutical Care School of Pharmaceutical Sciences, University of Phayao Phayao ThailandDepartment of Pharmaceutical Care Faculty of Pharmacy, Chiang Mai University Chiang Mai ThailandABSTRACT Sitafloxacin is one of the oral respiratory quinolones for the treatment of community‐acquired pneumonia. The pharmacokinetic (PK) changes of sitafloxacin in critical illness have been previously reported. However, sitafloxacin exposure and target attainment have never been confirmed in this population. To develop a population pharmacokinetic (PK) model of sitafloxacin, plasma and epithelial lining fluid (ELF) concentrations were obtained after sitafloxacin administration as a 200‐mg single dose under fasting condition in 12 subjects. A population pharmacokinetic analysis was performed using a nonlinear mixed‐effects modeling approach. The probability of target attainment (PTA) and cumulative fraction of response (CFR) against the MIC distribution of S. pneumoniae isolated from Thai patients was estimated by Monte Carlo simulations. The pharmacokinetics of sitafloxacin in plasma was best described by a one‐compartment model linking to the ELF compartment. The partition coefficient which relates drug exposure in ELF to drug exposure in plasma was estimated to be 0.77. Age was a significant covariate that impacted the relative bioavailability. Results from Monte Carlo simulations showed that the maximum approved dose of sitafloxacin 100 mg q 12 h provided > 90% PTA and CFR in both plasma and ELF. The current maximal dosing of sitafloxacin provided adequate exposure in plasma and ELF for the treatment of critically ill Thai patients with pneumonia.https://doi.org/10.1002/prp2.70081alveolar epithelial lining fluidcritically ill patientsMonte Carlo simulationspopulation pharmacokineticsSitafloxacin |
| spellingShingle | Taniya Paiboonvong Preecha Montakantikul Navarat Panjasawatwong Noppaket Singkham Baralee Punyawudho Population Pharmacokinetics and Pharmacodynamics of Sitafloxacin in Plasma and Alveolar Epithelial Lining Fluid of Critically Ill Thai Patients With Pneumonia Pharmacology Research & Perspectives alveolar epithelial lining fluid critically ill patients Monte Carlo simulations population pharmacokinetics Sitafloxacin |
| title | Population Pharmacokinetics and Pharmacodynamics of Sitafloxacin in Plasma and Alveolar Epithelial Lining Fluid of Critically Ill Thai Patients With Pneumonia |
| title_full | Population Pharmacokinetics and Pharmacodynamics of Sitafloxacin in Plasma and Alveolar Epithelial Lining Fluid of Critically Ill Thai Patients With Pneumonia |
| title_fullStr | Population Pharmacokinetics and Pharmacodynamics of Sitafloxacin in Plasma and Alveolar Epithelial Lining Fluid of Critically Ill Thai Patients With Pneumonia |
| title_full_unstemmed | Population Pharmacokinetics and Pharmacodynamics of Sitafloxacin in Plasma and Alveolar Epithelial Lining Fluid of Critically Ill Thai Patients With Pneumonia |
| title_short | Population Pharmacokinetics and Pharmacodynamics of Sitafloxacin in Plasma and Alveolar Epithelial Lining Fluid of Critically Ill Thai Patients With Pneumonia |
| title_sort | population pharmacokinetics and pharmacodynamics of sitafloxacin in plasma and alveolar epithelial lining fluid of critically ill thai patients with pneumonia |
| topic | alveolar epithelial lining fluid critically ill patients Monte Carlo simulations population pharmacokinetics Sitafloxacin |
| url | https://doi.org/10.1002/prp2.70081 |
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