Population pharmacokinetics of polymyxin B: a systematic review

Chen, Na; Guo, Jianhao; Xie, Jiao; Xu, M.; Xing, Hao; Ma, Kuifen; Rao, Yuefeng

doi:10.21037/atm-22-236

Cited by 15 publications

(9 citation statements)

References 23 publications

(52 reference statements)

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“…In the present study, the estimated typical value of CL was 1.50 L/h for colistin sulfate, which was lower than the CL of colistin converted from CMS (2.92 L/h) (Couet et al, 2011), and similar to the CL of polymyxin B reported previously (range 1.59-2.86 L/h) (Wang et al, 2021;Chen et al, 2022). CrCL was identified to have a significant effect on the CL of colistin sulfate, which was in agreement with a previous study (Yu et al, 2022) and the disposition characteristic of polymyxin B (Wang et al, 2020;Li et al, 2021b;Yu et al, 2021).…”

Section: Discussionsupporting

confidence: 81%

“…Our results showed that a two-compartment model with first-order elimination best fitted the PK of colistin sulfate in critically ill patients, which was inconsistent with a previous study in which a one-compartment model with linear-elimination was used to describe the pharmacokinetic characteristics of colistin sulfate ( Yu et al, 2022 ). This could be due to the intensive combined scattered sampling strategy used in the current study ( Chen et al, 2022 ). We collected 6-8 blood samples from six patients across the distribution and elimination phases of colistin sulfate in dosing intervals, which fits to better describe the characteristics of distribution for colistin sulfate in humans ( Li et al, 2021a ).…”

Section: Discussionmentioning

confidence: 99%

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Population pharmacokinetics of intravenous colistin sulfate and dosage optimization in critically ill patients

Jin

Yan

et al. 2022

Front. Pharmacol.

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Aims: To explore the population pharmacokinetics of colistin sulfate and to optimize the dosing strategy for critically ill patients.Methods: The study enrolled critically ill adult patients who received colistin sulfate intravenously for more than 72 h with at least one measurement of plasma concentration. Colistin concentrations in plasma or urine samples were measured by ultraperformance liquid chromatography tandem mass spectrometry (LC-MS/MS). The population pharmacokinetics (PPK) model for colistin sulfate was developed using the Phoenix NLME program. Monte Carlo simulation was conducted to evaluate the probability of target attainment (PTA) for optimizing dosing regimens.Results: A total of 98 plasma concentrations from 20 patients were recorded for PPK modeling. The data were adequately described by a two-compartment model with linear elimination. During modeling, creatinine clearance (CrCL) and alanine aminotransferase (ALT) were identified as covariates of the clearance (CL) and volume of peripheral compartment distribution (V2), respectively. In addition, colistin sulfate was predominantly cleared by the nonrenal pathway with a median urinary recovery of 10.05% with large inter-individual variability. Monte Carlo simulations revealed a greater creatinine clearance associated with a higher risk of sub-therapeutic exposure to colistin sulfate. The target PTA (≥90%) of dosage regimens recommended by the label sheet was achievable only in patients infected by pathogens with MIC ≤0.5 mg/L or with renal impairments.Conclusion: Our study showed that the dose of intravenous colistin sulfate was best adjusted by CrCL and ALT. Importantly, the recommended dosing regimen of 1.0–1.5 million units daily was insufficient for patients with normal renal functions (CrCL ≥80 ml/min) or those infected by pathogens with MIC ≥1.0 mg/L. The dosage of colistin sulfate should be adjusted according to renal function and drug exposure.

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Section: Discussionsupporting

confidence: 81%

Section: Discussionmentioning

confidence: 99%

Population pharmacokinetics of intravenous colistin sulfate and dosage optimization in critically ill patients

Jin

Yan

et al. 2022

Front. Pharmacol.

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“…Once daily dose is associated with AKI, it is expected that polymyxin B concentrations also be associated with AKI. However, a direct correlation between polymyxin B exposure and response/toxicity has not been well demonstrated [ 11 – 15 ]. Previously, we found that AUC ss,24 h of > 100 mg h/L was a good predictor of the probability of nephrotoxicity ( P = 0.001) [ 16 ].…”

Section: Introductionmentioning

confidence: 99%

An area under the concentration–time curve threshold as a predictor of efficacy and nephrotoxicity for individualizing polymyxin B dosing in patients with carbapenem-resistant gram-negative bacteria

Yang

Liu

et al. 2022

Crit Care

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Background Evidence supports therapeutic drug monitoring of polymyxin B, but clinical data for establishing an area under the concentration–time curve across 24 h at steady state (AUCss,24 h) threshold are still limited. This study aimed to examine exposure–response/toxicity relationship for polymyxin B to establish an AUCss,24 h threshold in a real-world cohort of patients. Methods Using a validated Bayesian approach to estimate AUCss,24 h from two samples, AUCss,24 h threshold that impacted the risk of polymyxin B-related nephrotoxicity and clinical response were derived by classification and regression tree (CART) analysis and validated by Cox regression analysis and logical regression analysis. Results A total of 393 patients were included; acute kidney injury (AKI) was 29.0%, clinical response was 63.4%, and 30-day all-cause mortality was 35.4%. AUCss,24 h thresholds for AKI of > 99.4 mg h/L and clinical response of > 45.7 mg h/L were derived by CART analysis. Cox and logical regression analyses showed that AUCss,24 h of > 100 mg h/L was a significant predictor of AKI (HR 16.29, 95% CI 8.16–30.25, P < 0.001) and AUCss,24 h of ≥ 50 mg h/L (OR 4.39, 95% CI 2.56–7.47, P < 0.001) was independently associated with clinical response. However, these exposures were not associated with mortality. In addition, the correlation between trough concentration (1.2–2.8 mg/L) with outcomes was similar to AUCss,24 h. Conclusions For critically ill patients, AUCss,24 h threshold of 50–100 mg h/L was associated with decreased nephrotoxicity while assuring clinical efficacy. Therapeutic drug monitoring is recommended for individualizing polymyxin B dosing.

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“…Polymyxin B can be administered intravenously, intrathecally, or by aerosol inhalation ( Tsuji et al, 2019 ), with a half-life of about 9–11.5 h after being administered intravenously, and a steady-state volume of distribution of about 12.7–34.3 L ( Chen et al, 2022 ). The urinary recovery of polymyxin B is low and non-renal clearance is considered the major route of the clearance of polymyxin B ( Tsuji et al, 2019 ), but it undergoes extensive reabsorption by renal tubular cells ( Nang et al, 2021 ).…”

Section: Introductionmentioning

confidence: 99%

Population pharmacokinetic analysis, renal safety, and dosing optimization of polymyxin B in lung transplant recipients with pneumonia: A prospective study

et al. 2022

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Objectives: This study aims to characterize the population pharmacokinetics of polymyxin B in lung transplant recipients and optimize its dosage regimens.Patients and methods: This prospective study involved carbapenem-resistant organisms-infected patients treated with polymyxin B. The population pharmacokinetic model was developed using the NONMEM program. The clinical outcomes including clinical treatment efficacy, microbiological efficacy, nephrotoxicity, and hyperpigmentation were assessed. Monte Carlo simulation was performed to calculate the probability of target attainment in patients with normal or decreased renal function.Results: A total of 34 hospitalized adult patients were included. 29 (85.29%) patients were considered of clinical cure or improvement; 14 (41.18%) patients had successful bacteria elimination at the end of the treatment. Meanwhile, 5 (14.71%) patients developed polymyxin B-induced nephrotoxicity; 19 (55.88%) patients developed skin hyperpigmentation. A total of 164 concentrations with a range of 0.56–11.66 mg/L were obtained for pharmacokinetic modeling. The pharmacokinetic characteristic of polymyxin B was well described by a 1-compartment model with linear elimination, and only creatinine clearance was identified as a covariate on the clearance of polymyxin B. Monte Carlo simulations indicated an adjusted dosage regimen might be needed in patients with renal insufficiency and the currently recommended dose regimens by the label sheet of polymyxin B may likely generate a subtherapeutic exposure for MIC = 2 mg/L.Conclusion: Renal function has a significant effect on the clearance of polymyxin B in lung transplant recipients, and an adjustment of dosage was needed in patients with renal impairments.

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Population pharmacokinetics of polymyxin B: a systematic review

Cited by 15 publications

References 23 publications

Population pharmacokinetics of intravenous colistin sulfate and dosage optimization in critically ill patients

Population pharmacokinetics of intravenous colistin sulfate and dosage optimization in critically ill patients

An area under the concentration–time curve threshold as a predictor of efficacy and nephrotoxicity for individualizing polymyxin B dosing in patients with carbapenem-resistant gram-negative bacteria

Population pharmacokinetic analysis, renal safety, and dosing optimization of polymyxin B in lung transplant recipients with pneumonia: A prospective study

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