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• W2085958466 startingPage "2497" @default.
• W2085958466 abstract "Respiratory tract infections cause 90% of premature mortality in patients with cystic fibrosis (CF). Treatment of Pseudomonas aeruginosa infection is often very problematic. Piperacillin-tazobactam has good activity against P. aeruginosa, but its pharmacokinetics (PK) in CF patients has not been compared to the PK in healthy volunteers in a controlled clinical study. Therefore, we compared the population PK and pharmacodynamics (PD) of piperacillin between CF patients and healthy volunteers. We studied 8 adult (median age, 20 years) CF patients (average total body weight [WT], 43.1 +/- 7.8 kg) and 26 healthy volunteers (WT, 71.1 +/- 11.8 kg) who each received 4 g piperacillin as a 5-min intravenous infusion. We determined piperacillin levels by high-performance liquid chromatography, and we used NONMEM for population PK and Monte Carlo simulation. We used a target time of nonprotein-bound concentration above the MIC of 50%, which represents near-maximal bacterial killing. Unscaled total clearance was 25% lower, and the volume of distribution was 31% lower in CF patients. Allometric scaling by lean body mass reduced the unexplained (random) between-subject variability in clearance by 26% compared to the variability of linear scaling by WT. A standard dosage regimen of 3 g/70 kg body WT every 4 h as a 30-min infusion (daily dose, 18 g) achieved a robust (> or =90%) probability-of-target attainment (PTA) for MICs of < or =12 mg/liter in CF patients and < or =16 mg/liter in healthy volunteers. Alternative modes of administration allowed a marked dose reduction to 9 g daily. Prolonged (4-h) infusions of 3 g/70 kg WT every 8 h and continuous infusion (daily dose, 9 g), achieved a robust PTA for MICs of < or =16 mg/liter in both groups. Piperacillin achieved PTA expectation values of 64% and 89% against P. aeruginosa infection in CF patients, based on susceptibility data from two German CF clinics." @default.
• W2085958466 created "2016-06-24" @default.
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• W2085958466 date "2007-07-01" @default.
• W2085958466 modified "2023-10-17" @default.
• W2085958466 title "Systematic Comparison of the Population Pharmacokinetics and Pharmacodynamics of Piperacillin in Cystic Fibrosis Patients and Healthy Volunteers" @default.
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• W2085958466 doi "https://doi.org/10.1128/aac.01477-06" @default.
• W2085958466 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/1913222" @default.
• W2085958466 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/17485505" @default.
• W2085958466 hasPublicationYear "2007" @default.
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