Single-Dose Pharmacokinetics of Aztreonam in Healthy Volunteers and Renal Failure Patients

Guinaidy, M. A. El; Nawishy, S; Bary, M.; Sabbour, M. M.

doi:10.1080/1120009x.1989.11738886

Cited by 8 publications

(17 citation statements)

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“…Individual aztreonam concentrations and relevant covariates (age, weight, height, serum creatinine concentration) were obtained from 2 aztreonam clinical studies in healthy male volunteers with normal renal function or various degrees of renal impairment. In the study by Mihindu et al, 24 male volunteers were included, and plasma samples were collected 0.16, 0.33, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, and 48 hours after dosing.…”

Section: Methodsmentioning

confidence: 99%

“…Information on population and demographics is included in Table . Further details on these 2 studies have been reported previously …”

Section: Methodsmentioning

confidence: 99%

“…The aztreonam prescribing information, dosage, and dosing interval determined by the causative organisms and severity of the infection were used in the simulation. Simulations of 1000 subjects were conducted according to each renal function group, subjects with normal renal function (CRCL > 80 mL/min/1.73 m 2 ), mild renal impairment (CrCL 30–80 mL/min/1.73 m 2 ), moderate renal impairment (CrCL 10–30 mL/min/1.73m 2 ), and severe renal impairment (CrCL< 10 mL/min/1.73 m 2 ) . A loading dose of 1 or 2 g of aztreonam intravenously infused within 30 minutes was applied for all patients.…”

Section: Methodsmentioning

confidence: 99%

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Evaluation of Aztreonam Dosing Regimens in Patients With Normal and Impaired Renal Function: A Population Pharmacokinetic Modeling and Monte Carlo Simulation Analysis

Zhou

et al. 2016

The Journal of Clinical Pharma

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Aztreonam is a monocyclic β-lactam antibiotic often used to treat infections caused by Enterobacteriaceae or Pseudomonas aeruginosa. Despite the long history of clinical use, population pharmacokinetic modeling of aztreonam in renally impaired patients is not yet available. The aims of this study were to assess the impact of renal impairment on aztreonam exposure and to evaluate dosing regimens for patients with renal impairment. A population model describing aztreonam pharmacokinetics following intravenous administration was developed using plasma concentrations from 42 healthy volunteers and renally impaired patients from 2 clinical studies. The final pharmacokinetic model was used to predict aztreonam plasma concentrations and evaluate the probability of pharmacodynamic target attainment (PTA) in patients with different levels of renal function. A 2-compartment model with first-order elimination adequately described aztreonam pharmacokinetics. The population mean estimates of aztreonam clearance, intercompartmental clearance, volume of distribution of the central compartment, and volume of distribution of the peripheral compartment were 4.93 L/h, 9.26 L/h, 7.43 L, and 6.44 L, respectively. Creatinine clearance and body weight were the most significant variables to explain patient variability in aztreonam clearance and volume of distribution, respectively. Simulations using the final pharmacokinetic model resulted in a clinical susceptibility break point of 4 and 8 mg/L, respectively, based on the clinical use of 1- and 2-g loading doses with the same or reduced maintenance dose every 8 hours for various renal deficiency patients. The population pharmacokinetic modeling and PTA estimation support adequate PTAs (>90% PTA) from the aztreonam label for dose adjustment of aztreonam in patients with moderate and severe renal impairment.

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Section: Methodsmentioning

confidence: 99%

“…Information on population and demographics is included in Table . Further details on these 2 studies have been reported previously …”

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Evaluation of Aztreonam Dosing Regimens in Patients With Normal and Impaired Renal Function: A Population Pharmacokinetic Modeling and Monte Carlo Simulation Analysis

Zhou

et al. 2016

The Journal of Clinical Pharma

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“…The aztreonam population pharmacokinetic model involving 11 male volunteers with CL CR values of Ͻ10 ml/min/1.73 m 2 , based on the Cockcroft-Gault formula, was described previously (6)(7)(8). In those studies, aztreonam serum concentrations were determined at standard times after a single 1-g dose; patients did not receive dialysis during the sampling period (7,8). MCS was conducted as described previously (6).…”

mentioning

confidence: 99%

“…Body weight was a significant covariate in the population pharmacokinetic model. In the MCS, the body weight for each of the 1,000 patients was sampled based on the body weight distribution (mean, 71.4 kg; standard deviation [SD], 11.7 kg) for patients with CL CR values of Ͻ10 ml/min/1.73 m 2 (7,8). Three dosing strategies (1 g or 2 g once daily or 2 g thrice weekly [days 1, 3, and 5], using a 30-min intravenous infusion for all regimens) were used in the simulation.…”

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confidence: 99%

Simplified Aztreonam Dosing in Patients with End-Stage Renal Disease: Results of a Monte Carlo Simulation

Gross

Zhou

et al. 2018

Antimicrob Agents Chemother

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The manufacturer-recommended aztreonam dosing for patients with creatinine clearance values of <10 ml/min/1.73 m is complex. It is not known whether simpler posthemodialysis dosing administered once daily or thrice weekly can reliably achieve pharmacodynamic goals. We found that 1 or 2 g administered once daily after hemodialysis had >90% probability of target attainment up to MICs of 4 or 8 mg/liter, respectively. Thrice-weekly dosing should generally be avoided, except in nonsevere infections with MICs of ≤0.5 mg/liter.

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Preliminary physiologically based pharmacokinetic modeling of renally cleared drugs in Chinese pregnant women

Lee

et al. 2020

Biopharm & Drug Disp

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AimThe aim of this study was to build and verify a preliminary physiologically based pharmacokinetic (PBPK) model of Chinese pregnant women. The model was used to predict maternal pharmacokinetics (PK) of 6 predominantly renally cleared drugs.MethodBased on SimCYP Caucasian pregnancy population dataset, the preliminary Chinese pregnant population was built by updating several key parameters and equations according to physiological parameters of Chinese (or Japanese) pregnant women. Drug‐specific parameters of 6 renally cleared drugs were validated through PBPK modeling of Caucasian non‐pregnant, Caucasian pregnant and Chinese non‐pregnant population. The preliminary PBPK model of Chinese pregnant population was then developed by integrating the preliminary Chinese pregnant population and the drug‐specific parameters. This model was verified by comparing the predicted maternal PK of these 6 drugs with the observed in vivo data from the literature.ResultsThe preliminary Chinese pregnant population PBPK model successfully predicted the PK of 6 target drugs for different pregnancy stages. The predicted plasma concentrations time profiles fitted the observed data well, and most predicted PK parameters were within 2‐fold of observed data. Conclusions: The preliminary Chinese pregnant population PBPK model provided a useful tool to predict the maternal PK of 6 predominantly renally cleared drugs in Chinese pregnant women.

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Single-Dose Pharmacokinetics of Aztreonam in Healthy Volunteers and Renal Failure Patients

Cited by 8 publications

References 8 publications

Evaluation of Aztreonam Dosing Regimens in Patients With Normal and Impaired Renal Function: A Population Pharmacokinetic Modeling and Monte Carlo Simulation Analysis

Evaluation of Aztreonam Dosing Regimens in Patients With Normal and Impaired Renal Function: A Population Pharmacokinetic Modeling and Monte Carlo Simulation Analysis

Simplified Aztreonam Dosing in Patients with End-Stage Renal Disease: Results of a Monte Carlo Simulation

Preliminary physiologically based pharmacokinetic modeling of renally cleared drugs in Chinese pregnant women

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