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Population Pharmaco...
Population Pharmacokinetics of Piperacillin in Sepsis Patients : Should Alternative Dosing Strategies Be Considered?
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- Andersen, Maria Goul (författare)
- Aarhus Univ Hosp, Dept Infect Dis, Aarhus, Denmark
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- Thorsted, Anders (författare)
- Uppsala universitet,Institutionen för farmaceutisk biovetenskap
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- Storgaard, Merete (författare)
- Aarhus Univ Hosp, Dept Infect Dis, Aarhus, Denmark
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- Kristoffersson, Anders N., 1985- (författare)
- Uppsala universitet,Institutionen för farmaceutisk biovetenskap
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- Friberg, Lena E (författare)
- Uppsala universitet,Institutionen för farmaceutisk biovetenskap
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- Öbrink-Hansen, Kristina (författare)
- Aarhus Univ Hosp, Dept Infect Dis, Aarhus, Denmark
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(creator_code:org_t)
- American Society for Microbiology, 2018
- 2018
- Engelska.
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Ingår i: Antimicrobial Agents and Chemotherapy. - : American Society for Microbiology. - 0066-4804 .- 1098-6596. ; 62:5
- Relaterad länk:
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- Sufficient antibiotic dosing in septic patients is essential for reducing mortality. Piperacillin-tazobactam is often used for empirical treatment, but due to the pharmacokinetic (PK) variability seen in septic patients, optimal dosing may be a challenge. We determined the PK profile for piperacillin given at 4 g every 8 h in 22 septic patients admitted to a medical ward. Piperacillin concentrations were compared to the clinical breakpoint MIC for Pseudomonas aeruginosa (16 mg/liter), and the following PK/pharmacodynamic (PD) targets were evaluated: the percentage of the dosing interval that the free drug concentration is maintained above the MIC (fTMIC) of 50% and 100%. A two-compartment population PK model described the data well, with clearance being divided into renal and nonrenal components. The renal component was proportional to the estimated creatinine clearance (eCLCR) and constituted 74% of the total clearance in a typical individual (eCLCR, 83.9 ml/min). Patients with a high eCLCR (>130 ml/min) were at risk of subtherapeutic concentrations for the current regimen, with a 90% probability of target attainment being reached at MICs of 2.0 (50% fTMIC) and 0.125 mg/liter (100% fTMIC). Simulations of alternative dosing regimens and modes of administration showed that dose increment and prolonged infusion increased the chance of achieving predefined PK/PD targets. Alternative dosing strategies may therefore be needed to optimize piperacillin exposure in septic patients. (This study has been registered at ClinicalTrials.gov under identifier NCT02569086.)
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Infektionsmedicin (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Infectious Medicine (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Farmaceutiska vetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Pharmaceutical Sciences (hsv//eng)
Nyckelord
- augmented renal clearance
- dosage optimization
- piperacillin
- population pharmacokinetics
- sepsis
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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