Trial reportBritish journal of clinical pharmacology2008
Inhibition of flucloxacillin tubular renal secretion by piperacillin.
Trial report in British journal of clinical pharmacology, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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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.
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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.
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Who cites it
17 citing papers in PubMed, 37 citations in OpenAlex.
- Competitive inhibition of renal tubular secretion of gemifloxacin by probenecid.Antimicrobial agents and chemotherapy · 2009Trial
- Relationship between nephrotoxicity and area under the concentration-time curve of vancomycin in critically ill patients: a multicenter retrospective study.Microbiology spectrum · 2024Observational
- Combination with a FtsZ inhibitor potentiates the in vivo efficacy of oxacillin against methicillin-resistantMedicinal chemistry research : an international journal for rapid communications on design and mechanisms of action of biologically active agents · 2022Article
- Association of vancomycin plus piperacillin-tazobactam with early changes in creatinine versus cystatin C in critically ill adults: a prospective cohort study.Intensive care medicine · 2022Article
- Acute kidney injury in villous cancer patients treated with vancomycin and tazobactam/piperacillin.Clinical case reports · 2022Article
- Acute kidney injury following prophylactic flucloxacillin and gentamicin in primary hip and knee arthroplasty.Clinical kidney journal · 2021Article
- Evaluation of the risk of acute kidney injury with the use of piperacillin/tazobactam among adult critically ill patients.Infection · 2020Article
- Paclitaxel, Imatinib and 5-Fluorouracil Increase the Unbound Fraction of Flucloxacillin In Vitro.Antibiotics (Basel, Switzerland) · 2020Article
- Article
- Novel Population Pharmacokinetic Approach to Explain the Differences between Cystic Fibrosis Patients and Healthy Volunteers via Protein Binding.Pharmaceutics · 2019Article
- Incidence of Acute Kidney Injury Among Critically Ill Patients With Brief Empiric Use of Antipseudomonal β-Lactams With Vancomycin.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2019Article
- Association of Acute Kidney Injury With Concomitant Vancomycin and Piperacillin/Tazobactam Treatment Among Hospitalized Children.JAMA pediatrics · 2017Article
- Renal Drug Transporters and Drug Interactions.Clinical pharmacokinetics · 2017Review
- Predictors of Acute Kidney Injury in Neurocritical Care Patients Receiving Continuous Hypertonic Saline.The Neurohospitalist · 2017Article
- Mechanistic models describing active renal reabsorption and secretion: a simulation-based study.The AAPS journal · 2013Article
- Article
- Pharmacokinetic drug interactions of antimicrobial drugs: a systematic review on oxazolidinones, rifamycines, macrolides, fluoroquinolones, and Beta-lactams.Pharmaceutics · 2011Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aimsTo explore the extent, time course, site(s), mechanism and possible clinical relevance of the pharmacokinetic (PK) interaction between piperacillin and flucloxacillin.
methodsA single-dose, randomized, six-way crossover study in 10 healthy volunteers where all subjects received all of the following as 5-min intravenous infusions: (i) 1.5 g piperacillin, (ii) 0.5 g flucloxacillin, (iii) 1.5 g piperacillin + 0.5 g flucloxacillin, (iv) 3 g piperacillin, (v) 1 g flucloxacillin, and (vi) 3 g piperacillin + 1 g flucloxacillin. Drug concentrations in plasma and urine were determined by high-performance liquid chromatography. WinNonlin was used for PK modelling and statistics.
resultsPiperacillin significantly decreased the renal clearance of flucloxacillin from 5.44 to 2.29 l h(-1) (medians, P < 0.01) and the nonrenal clearance of flucloxacillin from 2.67 to 1.80 l h(-1) (P < 0.01). The renal clearance of flucloxacillin was reduced to 45% (point estimate, 90% confidence interval 40 to 50%) and the nonrenal clearance to 66% (59, 73). The extent of interaction was larger at the higher doses. Competitive inhibition of tubular secretion by piperacillin was identified as the most likely mechanism for the decreased renal clearance of flucloxacillin. Piperacillin had a 15-times higher affinity for the renal transporter than flucloxacillin based on the molar ratio. Piperacillin PK was only slightly affected by flucloxacillin.
conclusionsPiperacillin inhibits renal and nonrenal elimination of flucloxacillin. This interaction seems clinically significant, as total clearance was reduced by a factor of 1.5 for the lower and 2.1 for the higher doses. PK interactions, especially with piperacillin, are likely to occur also with other beta-lactam combinations and might be useful to improve the effectiveness of antibacterial treatment.
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