Trial reportAntimicrobial agents and chemotherapy2012
Population pharmacokinetics of piperacillin at two dose levels: influence of nonlinear pharmacokinetics on the pharmacodynamic profile.
Trial report in Antimicrobial agents and chemotherapy, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers, 3 of them syntheses that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
20 citing papers in PubMed, 3 syntheses or guidelines pooled it.
- Pharmacokinetics of Commonly Used Medications in Children Receiving Continuous Renal Replacement Therapy: A Systematic Review of Current Literature.Clinical pharmacokinetics · 2022Pooled it
- Antibiotics in Adult Cystic Fibrosis Patients: A Review of Population Pharmacokinetic Analyses.Clinical pharmacokinetics · 2021Pooled it
- Scaling beta-lactam antimicrobial pharmacokinetics from early life to old age.British journal of clinical pharmacology · 2019Pooled it
- A Pooled Pharmacokinetic Analysis for Piperacillin/Tazobactam Across Different Patient Populations: From Premature Infants to the Elderly.Clinical pharmacokinetics · 2025Article
- Balancing the scales: achieving the optimal beta-lactam to beta-lactamase inhibitor ratio with continuous infusion piperacillin/tazobactam against extended spectrum beta-lactamase producingAntimicrobial agents and chemotherapy · 2024Article
- Predictive Factors of Piperacillin Exposure and the Impact on Target Attainment after Continuous Infusion Administration to Critically Ill Patients.Antibiotics (Basel, Switzerland) · 2023Article
- Population Pharmacokinetics of Piperacillin/Tazobactam Across the Adult Lifespan.Clinical pharmacokinetics · 2023Article
- Individualized antibiotic dosage regimens for patients with augmented renal clearance.Frontiers in pharmacology · 2023Review
- Using a Validated Population Pharmacokinetic Model for Dosing Recommendations of Continuous Infusion Piperacillin for Critically Ill Adult Patients.Clinical pharmacokinetics · 2022Article
- Comparison of Piperacillin and Tazobactam Pharmacokinetics in Critically Ill Patients with Trauma or with Burn.Antibiotics (Basel, Switzerland) · 2022Article
- Personalized Antibiotic Therapy for the Critically Ill: Implementation Strategies and Effects on Clinical Outcome of Piperacillin Therapeutic Drug Monitoring-A Descriptive Retrospective Analysis.Antibiotics (Basel, Switzerland) · 2021Article
- Piperacillin-Tazobactam in Intensive Care Units: A Review of Population Pharmacokinetic Analyses.Clinical pharmacokinetics · 2021Review
- A mutation in the glycosyltransferase gene lafB causes daptomycin hypersusceptibility in Enterococcus faecium.The Journal of antimicrobial chemotherapy · 2020Article
- Novel Population Pharmacokinetic Approach to Explain the Differences between Cystic Fibrosis Patients and Healthy Volunteers via Protein Binding.Pharmaceutics · 2019Article
- Four Decades of β-Lactam Antibiotic Pharmacokinetics in Cystic Fibrosis.Clinical pharmacokinetics · 2019Review
- Pharmacodynamic model for β-lactam regimens used in surgical prophylaxis: model-based evaluation of standard dosing regimens.International journal of clinical pharmacy · 2018Article
- Population Pharmacokinetics of Piperacillin in Sepsis Patients: Should Alternative Dosing Strategies Be Considered?Antimicrobial agents and chemotherapy · 2018Article
- Development of a Novel Multipenicillin Assay and Assessment of the Impact of Analyte Degradation: Lessons for Scavenged Sampling in Antimicrobial Pharmacokinetic Study Design.Antimicrobial agents and chemotherapy · 2018Article
- Urinary free cortisol assessment by liquid chromatography tandem mass spectrometry: a case study of ion suppression due to unacquainted administration of piperacillin.Biochemia medica · 2017Review
- Population pharmacokinetic analysis of piperacillin in burn patients.Antimicrobial agents and chemotherapy · 2014Article
Corrections and comments
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Authors and funding
8 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Piperacillin in combination with tazobactam is one of the most commonly used intravenous antibiotics. There is evidence for a possible saturable elimination of piperacillin. Therefore, the saturable elimination and its impact on the choice of optimal dosage regimens were quantified. In a randomized crossover study, 10 healthy volunteers received 1,500 mg and 3,000 mg of piperacillin as 5-min intravenous infusion. Population pharmacokinetics based on plasma and urine data were determined utilizing NONMEM and S-ADAPT. Probabilities of target attainment (PTAs) were compared for different models and dosage regimens, based on the target time of the non-protein-bound concentration above the MIC of at least 50% of the dosing interval. Total clearance of piperacillin was 18% (geometric mean ratio, 90% confidence interval, 11 to 24%) lower (P < 0.01), and renal clearance was 24% (9 to 37%) lower (P = 0.02) at the high compared to the low dose. The final model included first-order nonrenal elimination and parallel first-order and mixed-order renal elimination. Nonrenal clearance was 5.44 liter/h (coefficient of variation, 18%), first-order renal clearance was 4.42 liter/h (47%), and the maximum elimination rate of mixed-order renal elimination was 219 mg/h (84%), with a Michaelis-Menten constant of 36.1 mg/liter (112%). Compared to models with saturable elimination, a linear model predicted up to 10% lower population PTAs for high-dose short-term infusions (6 g every 8 h) and up to 4% higher population PTAs for low-dose continuous infusions (6 g/day). While renal elimination of piperacillin was saturable at therapeutic concentrations, the extent of saturation of nonrenal clearance was small. The influence of saturable elimination on PTAs for clinically relevant dosage regimens was relatively small.
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