Safety and pharmacokinetic evaluation of intravenous colistin methanesulfonate sodium in Japanese healthy male subjects

Mizuyachi, Kaori; Hara, Katsutoshi; Wakamatsu, Akira; Nohda, Shigeru; Hirama, Toshiyasu

doi:10.1185/03007995.2011.626557

Cited by 29 publications

(22 citation statements)

References 19 publications

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“…This discrepancy seems to be due to the difference in the apparent V of colistin, which was double the value estimated in our burn patients, while the apparent CL of colistin was similar. Both the t 1/2 (4.98 h) and apparent V (67.9 liters) obtained using noncompartmental analysis in a previous study in healthy volunteers (21) were lower than those estimated in this study, but the apparent CL was similar. In general, increased blood flow to the kidneys and liver in the hypermetabolic phase (beyond 48 h after the burn injury) (16) and massive hydration in the treatment process increase the CL and V of many antibiotics.…”

Section: Discussioncontrasting

confidence: 42%

Population Pharmacokinetic Analysis of Colistin in Burn Patients

Han

Jeon

Hong

et al. 2013

Antimicrob Agents Chemother

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cColistin is increasingly used as a salvage therapy for nosocomial infections caused by multidrug-resistant Gram-negative bacteria such as Pseudomonas aeruginosa and Acinetobacter baumannii. However, the available pharmacokinetic (PK) data for colistin are limited to guide dosing. The aim of this study was to develop a population PK model of colistin and to identify the optimal dosage regimens for burn patients. Fifty patients with burns ranging from 4% to 85% of total body surface area who had been treated with colistimethate sodium (CMS) were studied. CMS, which is hydrolyzed in vivo to an active metabolite, was intravenously administered every 12 h. Blood samples were collected at 0, 1, 2, 4, 6, and 8 h after more than five infusions to measure the colistin concentration using a liquid chromatography-tandem mass spectrometry (LC-MS/MS) system. The population PK model was developed using nonlinear mixed effect modeling (NONMEM, v. 6.2). A one-compartment linear PK model for colistin best described the data. The covariates included in the final model were creatinine clearance for the relative fraction of CMS converted into colistin and the presence of edema for the turnover rate constant of CMS converted into colistin. A steadystate 24-h area under the concentration-time curve was simulated from 1,000 virtual patients receiving 150 mg colistin base activity every 12 h using the final model. Relative to previous studies with critically ill patients, the elimination half-life of colistin (6.6 h) was much shorter, and continuous renal replacement therapy was not a significant covariate for any PK parameters.

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Section: Discussioncontrasting

confidence: 42%

Population Pharmacokinetic Analysis of Colistin in Burn Patients

Han

Jeon

Hong

et al. 2013

Antimicrob Agents Chemother

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“…49,50 This increase was explained by the parallel elevation in the apparent V d of colistin compared with the healthy subjects (81.1 L vs 67.9 L). CL R of colistin in healthy subjects is minimal (0.12 ml/minute/ kg) and neither this parameter nor CL T were significantly altered in the burn population.…”

Section: Colistinmentioning

confidence: 93%

Pharmacokinetics and Pharmacodynamics of Antibacterial and Antifungal Agents in Adult Patients With Thermal Injury

Ortwine

Pogue

Faris

2015

Journal of Burn Care & Research

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Patients with significant thermal injury are at a high risk for developing bacterial and fungal infections due to the loss of protective integument and often require lengthy treatment courses with anti-infective agents. Dosing of these agents in the burn population is challenging as these patients experience changes in their physiology around 48 hours postinjury. These changes include increased cardiac output, increased blood flow to the kidneys and liver, and decreased albumin production. These alterations in the physiology can lead to an increased drug clearance, higher volumes of distribution, and increased or decreased total drug exposure. Currently, there are no guidelines describing the most ideal method of dosing anti-infectives in this population, and most studies that have been published include only a small number of patients. The purpose of this review is to summarize the existing literature regarding the pharmacokinetics and pharmacodynamics of antibiotics and antifungal agents in the burn population and to provide dosing suggestions whenever possible. Not all antibiotics and antifungal agents have been studied, and further research is needed in this area in order to provide optimal care for patients with thermal injury.

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“…The time-concentration data of FM, AMK, and COL after single intravenous administration was derived from previous studies (Lanao et al, 1981; Garraffo et al, 1990; Sauermann et al, 2005; Mizuyachi et al, 2011). The regimens administrated by intravenous (I.V.)…”

Section: Methodsmentioning

confidence: 99%

“…The regimens administrated by intravenous (I.V.) infusion were simulated over 24 h: FM 8 g every 8 h (FM 8 g q8h) (Sauermann et al, 2005), AMK 7.5 mg/kg once-daily (AMK 7.5 mg/kg qd) (Lanao et al, 1981), AMK 15 mg/kg once-daily (AMK 15 mg/kg qd) (Garraffo et al, 1990), COL 75,000 IU/kg every 12 h (COL 75,000 IU/kg q12h) (Mizuyachi et al, 2011), FM (8 g q8h)/AMK (7.5 mg/kg qd), FM (8 g q8h)/AMK (7.5 mg/kg q12h), FM (8 g q8h)/AMK (15 mg/kg qd), FM (8 g q8h)/COL (75,000 IU/kg q12h) (The Supplemental Table 1 showed the pharmacokinetics parameters of different regimens and Supplemental Figure 2 showed the concentrations during the simulation).…”

Section: Methodsmentioning

confidence: 99%

In vitro Pharmacokinetics/Pharmacodynamics Evaluation of Fosfomycin Combined with Amikacin or Colistin against KPC2-Producing Klebsiella pneumoniae

Zhou

Guo

et al. 2017

Front. Cell. Infect. Microbiol.

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Objectives: The emergence of carbapenem-resistant Enterobacteriaceae, especially Klebsiella pneumoniae, has become a major concern in clinic settings. Combination therapy is gaining momentum to counter the secondary resistance and potential suboptimal efficacy of monotherapy. The aim of this study was to evaluate the bactericidal effect of fosfomycin (FM), amikacin (AMK), or colistin (COL) alone and combinations against KPC2-producing K. pneumoniae using dynamic model by simulating human pharmacokinetics in vitro.Methods: The Pharmacokinetics Auto Simulation System 400 system was employed to simulate different dosing regimens of FM, AMK, and COL alone and combination. Bacterial growth recovery time (RT) and the area between the control growth and antibacterial killing curves (IE) were used as unbiased and comprehensive means for determining the antimicrobial effect.Results: We observed that COL alone was much pronounced than FM or AMK against KPC-Kp. IE of FM (8 g every 8 h) plus AMK (15 mg/kg once-daily) and FM (8 g every 8 h) plus COL (75,000 IU/kg every 12 h) were higher (>170 and >200 LogCFU/mL·h−1, respectively) than that of monotherapies against sensitive strains. Of note, the rate of resistance was lower when using the combination of FM (8 g every 8 h) plus COL (75,000 IU/kg every 12 h) than using COL (75,000 IU/kg every 12 h) alone.Conclusions: The combination of FM (8 g every 8 h) plus AMK (15 mg/kg once-daily) and FM (8 g every 8 h) plus COL (75,000 IU/kg every 12 h) were effective at maximizing bacterial killing and suppressing emergence of resistance.

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Safety and pharmacokinetic evaluation of intravenous colistin methanesulfonate sodium in Japanese healthy male subjects

Abstract: CMS-Na was safely administered to healthy volunteers but resulted in transient increase of urinary N-acetyl-β-D-glucosaminidase (NAG) and protein. Based on this study, the highest recommended dose of CMS-Na had sufficient bacteriostatic effect.

Cited by 29 publications

References 19 publications

Population Pharmacokinetic Analysis of Colistin in Burn Patients

Population Pharmacokinetic Analysis of Colistin in Burn Patients

Pharmacokinetics and Pharmacodynamics of Antibacterial and Antifungal Agents in Adult Patients With Thermal Injury

In vitro Pharmacokinetics/Pharmacodynamics Evaluation of Fosfomycin Combined with Amikacin or Colistin against KPC2-Producing Klebsiella pneumoniae

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