The effect of piperacillin dose on elimination kinetics in renal impairment

  title={The effect of piperacillin dose on elimination kinetics in renal impairment},
  author={George R. Aronoff and Rebecca S. Sloan and Michael E. Brier and Friedrich C. Luft},
  journal={European Journal of Clinical Pharmacology},
SummaryThe effect of drug dose on piperacillin elimination kinetics was examined in 27 adult subjects with varying renal function. Piperacillin, 15 mg/kg or 60 mg/kg, was given by bolus intravenous injection. The elimination half-life (t1/2) increased five-fold and plasma clearance (Clp) decreased by 80% in patients with renal failure. Both parameters were dose dependent in patients with normal renal function, but not in patients with renal insufficiency. Piperacillin dose dependent elimination… 

Population Pharmacokinetics of Piperacillin at Two Dose Levels: Influence of Nonlinear Pharmacokinetics on the Pharmacodynamic Profile

While renal elimination of piperacillin was saturable at therapeutic concentrations, the extent of saturation of nonrenal clearance was small and the influence of saturable elimination on PTAs for clinically relevant dosage regimens was relatively small.

Nonlinear pharmacokinetics of piperacillin in healthy volunteers--implications for optimal dosage regimens.

Part of the renal elimination of piperacillin is saturable at clinically used doses, and a model with first-order nonrenal elimination and parallel first- order and mixed-order renal elimination had the best predictive performance.

Population Pharmacokinetics of Piperacillin in Sepsis Patients: Should Alternative Dosing Strategies Be Considered?

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, andAlternative dosing strategies may be needed to optimize piperacillin exposure in septic patients.

Identification of Optimal Renal Dosage Adjustments for Traditional and Extended-Infusion Piperacillin-Tazobactam Dosing Regimens in Hospitalized Patients

This study examined the effect of various levels of renal impairment on the probability of achieving free drug concentrations that exceed the MIC for 50% of the dosing interval (50% fT > MIC) for traditional and extended-infusion piperacillin-tazobactam (TZP) dosing strategies and identified optimal renal dosage adjustments that yielded probability of target attainment (PTA).

Pharmacokinetics of Intravenous Piperacillin Administration in Patients Undergoing On-Line Hemodiafiltration

  • K. OhC. Kim C. Ahn
  • Medicine, Biology
    Antimicrobial Agents and Chemotherapy
  • 2009
The pharmacokinetic characteristics of piperacillin sodium were studied in five volunteers undergoing on-line hemodiafiltration (HDF) and it is suggested the replacement of 500 mg of p Piperacillin after each on- line HDF session.

Population pharmacokinetics and pharmacodynamics of piperacillin/tazobactam in patients with complicated intra-abdominal infection.

Intermittent infusion and continuous infusion of piperacillin and tazobactam provided sufficient drug exposure to treat those pathogens commonly implicated in intra-abdominal infections.

Human variability in the renal elimination of foreign compounds and renal excretion-related uncertainty factors for risk assessment.

  • J. DorneK. WaltonA. Renwick
  • Medicine
    Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association
  • 2004

Evaluation of Drug Dosing in Renal Failure

The dosing of more than half of the medications that need dosing adjustment in CKD were not adjusted which can increase the side effects and toxicity of these drugs for CKD patients.

Suboptimal antimicrobial drug exposure in patients with renal impairment

Background Recommendations on drug dose adjustment in patients with renal impairment may vary between the references. It is often unknown which approach the dosing schemes were based on and what drug

Comparative Pharmacodynamics of Intermittent and Prolonged Infusions of Piperacillin/Tazobactam Using Monte Carlo Simulations and Steady-State Pharmacokinetic Data from Hospitalized Patients

At doses greater than or equal to 3.375 g every 8 hours, 4-hour infusions of piperacillin/tazobactam achieved excellent target attainment with lower daily doses compared with standard regimens at MICs less than orequal to 16 μg/mL.



Mezlocillin dose dependent elimination kinetics in renal impairment

Elimination was not prolonged by increasing the dose in subjects with normal renal function, but elimination kinetics were dose dependent in anuric patients.


Patients with chronic renal failure who received bolus doses of piperacillin maintained high serum levels for up to six hours. The percentage of the injected dose which was detectable in the urine in

Pharmacokinetics of piperacillin in patients with moderate renal failure and in patients undergoing hemodialysis

The pharmacokinetics of piperacillin administered intravenously were studied in patients with stable mild to moderate renal impairment and in five patients undergoing hemodialysis, implying significant nonrenal elimination.

Dose dependence of piperacillin pharmacokinetics.

The results document that piperacillin is subject to dose-dependent pharmacokinetics and Capacity-limited kinetics is a property shared by other ureidopenicillins.

Piperacillin: Human Pharmacokinetics After Intravenous and Intramuscular Administration

Probenecid (1 g given orally before administration of piperacillin) increased peak serum concentration, terminal serum half-life, and the area under the plasma concentration curve by 60%, and it decreased the apparent distribution volume and the renal clearance of the intramuscularly administered antibiotic by 40%.

Incidence and natural history of chemically defined varicella-zoster virus hepatitis in children and adolescents.

It is concluded that chemically defined VZV hepatitis is an infrequent, self-limiting complication of chickenpox in otherwise healthy children and adolescents.

Piperacillin, a new penicillin active against many bacteria resistant to other penicillins

  • K. FuH. Neu
  • Biology, Medicine
    Antimicrobial Agents and Chemotherapy
  • 1978
The in vitro activity of piperacillin, a new semisynthetic piperazine penicillin derivative, was evaluated against 626 clinical isolates and compared with the activity of other beta-lactam

In Vitro and In Vivo Antibacterial Activity of T-1220, a New Semisynthetic Penicillin

T-1220 is a new semisynthetic penicillin derivative that possesses a broad spectrum of in vitro antibacterial activity against gram-positive and gram-negative bacteria and is more effective than carbenicillin (CB-PC) against Pseudomonas aeruginosa, Klebsiella pneumoniae, Proteus species, and Serratia marcescens.

Piperacillin pharmacokinetics in subjects with chronic renal failure

A dose of 70 mg/kg or a dose of 4 g appears to provide adequate serum concentrations against susceptible organisms for a 12-h interval, and no adverse reactions were noted in any subject throughout the study.

Biliary concentrations of piperacillin in patients undergoing cholecystectomy

The biliary excretion of piperacillin was studied in patients undergoing cholecystectomy with marked activity against Pseudomonas aeruginosa and no correlation occurred with peak serum level of antibiotic, creatinine, bilirubin, or alkaline phosphatase.