ArticleBritish journal of clinical pharmacology2010
Nonlinear pharmacokinetics of piperacillin in healthy volunteers--implications for optimal dosage regimens.
Article in British journal of clinical pharmacology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed.
- Population pharmacokinetics of piperacillin at two dose levels: influence of nonlinear pharmacokinetics on the pharmacodynamic profile.Antimicrobial agents and chemotherapy · 2012Trial
- Early piperacillin exposure during continuous infusion in critically ill patients: the impact of renal and liver dysfunctions.Annals of intensive care · 2026Article
- Piperacillin Pharmacokinetics in a Pediatric Patient With Primary Hyperoxaluria Receiving High-Dose Continuous Dialysis Post Liver-Kidney Transplant.The journal of pediatric pharmacology and therapeutics : JPPT : the official journal of PPAG · 2025Article
- Population Pharmacokinetic Modeling of Piperacillin/Tazobactam in Healthy Adults and Exploration of Optimal Dosing Strategies.Pharmaceuticals (Basel, Switzerland) · 2025Article
- Model-informed dose optimization for prophylactic piperacillin-tazobactam in perioperative pediatric critically ill patients.Antimicrobial agents and chemotherapy · 2025Article
- A Pooled Pharmacokinetic Analysis for Piperacillin/Tazobactam Across Different Patient Populations: From Premature Infants to the Elderly.Clinical pharmacokinetics · 2025Article
- Population pharmacokinetic rationale for intravenous contezolid acefosamil followed by oral contezolid dosage regimens.Antimicrobial agents and chemotherapy · 2024Article
- Predicting Volume of Distribution in Neonates: Performance of Physiologically Based Pharmacokinetic Modelling.Pharmaceutics · 2023Article
- Comparison of Piperacillin and Tazobactam Pharmacokinetics in Critically Ill Patients with Trauma or with Burn.Antibiotics (Basel, Switzerland) · 2022Article
- Population Pharmacokinetic Model of Piperacillin in Critically Ill Patients and Describing Interethnic Variation Using External Validation.Antibiotics (Basel, Switzerland) · 2022Article
- Piperacillin-Tazobactam in Intensive Care Units: A Review of Population Pharmacokinetic Analyses.Clinical pharmacokinetics · 2021Review
- Pharmacokinetic and Pharmacodynamic Optimization of Antibiotic Therapy in Cystic Fibrosis Patients: Current Evidences, Gaps in Knowledge and Future Directions.Clinical pharmacokinetics · 2021Review
- Time above the MIC of Piperacillin-Tazobactam as a Predictor of Outcome in Pseudomonas aeruginosa Bacteremia.Antimicrobial agents and 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
- Using Population Pharmacokinetic Modeling and Monte Carlo Simulations To Determine whether Standard Doses of Piperacillin in Piperacillin-Tazobactam Regimens Are Adequate for the Management of Febrile Neutropenia.Antimicrobial agents and chemotherapy · 2017Article
- Population pharmacokinetic analysis of piperacillin in burn patients.Antimicrobial agents and chemotherapy · 2014Article
- Quantifying subpopulation synergy for antibiotic combinations via mechanism-based modeling and a sequential dosing design.Antimicrobial agents and chemotherapy · 2013Article
- Population pharmacokinetics of extended-infusion piperacillin-tazobactam in hospitalized patients with nosocomial infections.Antimicrobial agents and chemotherapy · 2012Article
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Authors and funding
6 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aims(i) To describe the first-order and mixed-order elimination pathways of piperacillin, (ii) to determine the between occasion variability (BOV) of pharmacokinetic parameters and (iii) to propose optimized dosage regimens.
methodsWe performed a five-period replicate dose study in four healthy volunteers. Each subject received 4g piperacillin as a single 5min intravenous infusion in each study period. Drug analysis was performed by HPLC. We used NONMEM and S-ADAPT for population pharmacokinetic analysis and Monte Carlo simulation to predict the probability of target attainment (PTA) with a target time of non-protein bound concentration above MIC >50% of the dosing interval.
resultsA model with first-order nonrenal elimination and parallel first-order and mixed-order renal elimination had the best predictive performance. For a 70kg subject we estimated 4.40lh(-1) for nonrenal clearance, 5.70lh(-1) for first-order renal clearance, 170mgh(-1) for V(max) , and 49.7mgl(-1) for K(m) for the mixed-order renal elimination. The BOV was 39% for V(max) , 117% for K(m) , and 8.5% for total clearance. A 30min infusion of 4g every 6h achieved robust (≥90%) PTAs for MICs ≤12mgl(-1) . As an alternative mode of administration, a 5h infusion of 6g every 8h achieved robust PTAs for MICs ≤48mgl(-1) .
conclusionsPart of the renal elimination of piperacillin is saturable at clinically used doses. The BOV of total clearance and volume of distribution were low. Prolonged infusions achieved better PTAs compared with shorter infusions at similar daily doses. This benefit was most pronounced for MICs between 12 and 48mgl(-1) .
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