Population Pharmacokinetics of Polymyxin B in Acutely Ill Adult Patients [Pharmacology]

Publication Date:
2018-02-24
Publisher:
The American Society for Microbiology (ASM)
Print ISSN:
0066-4804
Electronic ISSN:
1098-6596
Topics:
Biology
Medicine
Published by:
_version_ 1836398808717590528
autor Miglis, C., Rhodes, N. J., Avedissian, S. N., Kubin, C. J., Yin, M. T., Nelson, B. C., Pai, M. P., Scheetz, M. H.
beschreibung Polymyxin B (PB) has reemerged as a common treatment against multidrug-resistant Gram-negative pathogens. However, nephrotoxicity remains a significant dose-limiting side effect, and contemporary pharmacokinetic (PK) data are limited. This study sought to evaluate PB exposure differences in various loading and nonloading strategies according to total body weight (TBW) and adjusted body weight (ABW). Patients treated with PB had plasma samples obtained for clinical care and analyzed using liquid chromatography-tandem mass spectrometry. Compartmental PK models with linear and allometric scaling of TBW were explored. Semiparametric Monte Carlo simulation evaluated the total (i.e., protein bound plus unbound) area under the plasma concentration-time curve (AUC total ) during the first 24 h of therapy and at 96 h posttherapy for each regimen at the 10th, 50th, and 90th percentiles of TBW and ABW in the derivation cohort. Literature-based values of the 24-h total AUC/MIC ratio (AUC/MIC total ) of ≥50 defined efficacy, and literature-based values of the 72- to 96-h AUC total of ≥100 μg · h/ml defined toxicity. Fifty-two patients contributed 156 PB plasma samples. A two-compartment model with allometric scaling of TBW produced a comparable fit (Akaike information criterion [AIC] = 376.7) to that achieved with linear scaling (AIC = 378). The regimen of a loading dose of 2.5 mg/kg of body weight plus a fixed dose of 100 mg every 12 h had the highest probability of achieving a 24-h AUC/MIC total of ≥50 with the lowest probability of toxicity in all groups at 24 h, aside from those with the lowest 10th percentile of body weight. This is the first study to suggest that a weight-based loading and fixed maintenance (i.e., weight-independent) dosing strategy for polymyxin B may maximize efficacy while balancing toxicity concerns for most patients.
citation_standardnr 6173456
datenlieferant ipn_articles
feed_id 515
feed_publisher The American Society for Microbiology (ASM)
feed_publisher_url http://www.asm.org/
insertion_date 2018-02-24
journaleissn 1098-6596
journalissn 0066-4804
publikationsjahr_anzeige 2018
publikationsjahr_facette 2018
publikationsjahr_intervall 7984:2015-2019
publikationsjahr_sort 2018
publisher The American Society for Microbiology (ASM)
quelle Antimicrobial Agents and Chemotherapy
relation http://aac.asm.org/cgi/content/short/62/3/e01475-17?rss=1
search_space articles
shingle_author_1 Miglis, C., Rhodes, N. J., Avedissian, S. N., Kubin, C. J., Yin, M. T., Nelson, B. C., Pai, M. P., Scheetz, M. H.
shingle_author_2 Miglis, C., Rhodes, N. J., Avedissian, S. N., Kubin, C. J., Yin, M. T., Nelson, B. C., Pai, M. P., Scheetz, M. H.
shingle_author_3 Miglis, C., Rhodes, N. J., Avedissian, S. N., Kubin, C. J., Yin, M. T., Nelson, B. C., Pai, M. P., Scheetz, M. H.
shingle_author_4 Miglis, C., Rhodes, N. J., Avedissian, S. N., Kubin, C. J., Yin, M. T., Nelson, B. C., Pai, M. P., Scheetz, M. H.
shingle_catch_all_1 Population Pharmacokinetics of Polymyxin B in Acutely Ill Adult Patients [Pharmacology]
Polymyxin B (PB) has reemerged as a common treatment against multidrug-resistant Gram-negative pathogens. However, nephrotoxicity remains a significant dose-limiting side effect, and contemporary pharmacokinetic (PK) data are limited. This study sought to evaluate PB exposure differences in various loading and nonloading strategies according to total body weight (TBW) and adjusted body weight (ABW). Patients treated with PB had plasma samples obtained for clinical care and analyzed using liquid chromatography-tandem mass spectrometry. Compartmental PK models with linear and allometric scaling of TBW were explored. Semiparametric Monte Carlo simulation evaluated the total (i.e., protein bound plus unbound) area under the plasma concentration-time curve (AUC total ) during the first 24 h of therapy and at 96 h posttherapy for each regimen at the 10th, 50th, and 90th percentiles of TBW and ABW in the derivation cohort. Literature-based values of the 24-h total AUC/MIC ratio (AUC/MIC total ) of ≥50 defined efficacy, and literature-based values of the 72- to 96-h AUC total of ≥100 μg · h/ml defined toxicity. Fifty-two patients contributed 156 PB plasma samples. A two-compartment model with allometric scaling of TBW produced a comparable fit (Akaike information criterion [AIC] = 376.7) to that achieved with linear scaling (AIC = 378). The regimen of a loading dose of 2.5 mg/kg of body weight plus a fixed dose of 100 mg every 12 h had the highest probability of achieving a 24-h AUC/MIC total of ≥50 with the lowest probability of toxicity in all groups at 24 h, aside from those with the lowest 10th percentile of body weight. This is the first study to suggest that a weight-based loading and fixed maintenance (i.e., weight-independent) dosing strategy for polymyxin B may maximize efficacy while balancing toxicity concerns for most patients.
Miglis, C., Rhodes, N. J., Avedissian, S. N., Kubin, C. J., Yin, M. T., Nelson, B. C., Pai, M. P., Scheetz, M. H.
The American Society for Microbiology (ASM)
0066-4804
00664804
1098-6596
10986596
shingle_catch_all_2 Population Pharmacokinetics of Polymyxin B in Acutely Ill Adult Patients [Pharmacology]
Polymyxin B (PB) has reemerged as a common treatment against multidrug-resistant Gram-negative pathogens. However, nephrotoxicity remains a significant dose-limiting side effect, and contemporary pharmacokinetic (PK) data are limited. This study sought to evaluate PB exposure differences in various loading and nonloading strategies according to total body weight (TBW) and adjusted body weight (ABW). Patients treated with PB had plasma samples obtained for clinical care and analyzed using liquid chromatography-tandem mass spectrometry. Compartmental PK models with linear and allometric scaling of TBW were explored. Semiparametric Monte Carlo simulation evaluated the total (i.e., protein bound plus unbound) area under the plasma concentration-time curve (AUC total ) during the first 24 h of therapy and at 96 h posttherapy for each regimen at the 10th, 50th, and 90th percentiles of TBW and ABW in the derivation cohort. Literature-based values of the 24-h total AUC/MIC ratio (AUC/MIC total ) of ≥50 defined efficacy, and literature-based values of the 72- to 96-h AUC total of ≥100 μg · h/ml defined toxicity. Fifty-two patients contributed 156 PB plasma samples. A two-compartment model with allometric scaling of TBW produced a comparable fit (Akaike information criterion [AIC] = 376.7) to that achieved with linear scaling (AIC = 378). The regimen of a loading dose of 2.5 mg/kg of body weight plus a fixed dose of 100 mg every 12 h had the highest probability of achieving a 24-h AUC/MIC total of ≥50 with the lowest probability of toxicity in all groups at 24 h, aside from those with the lowest 10th percentile of body weight. This is the first study to suggest that a weight-based loading and fixed maintenance (i.e., weight-independent) dosing strategy for polymyxin B may maximize efficacy while balancing toxicity concerns for most patients.
Miglis, C., Rhodes, N. J., Avedissian, S. N., Kubin, C. J., Yin, M. T., Nelson, B. C., Pai, M. P., Scheetz, M. H.
The American Society for Microbiology (ASM)
0066-4804
00664804
1098-6596
10986596
shingle_catch_all_3 Population Pharmacokinetics of Polymyxin B in Acutely Ill Adult Patients [Pharmacology]
Polymyxin B (PB) has reemerged as a common treatment against multidrug-resistant Gram-negative pathogens. However, nephrotoxicity remains a significant dose-limiting side effect, and contemporary pharmacokinetic (PK) data are limited. This study sought to evaluate PB exposure differences in various loading and nonloading strategies according to total body weight (TBW) and adjusted body weight (ABW). Patients treated with PB had plasma samples obtained for clinical care and analyzed using liquid chromatography-tandem mass spectrometry. Compartmental PK models with linear and allometric scaling of TBW were explored. Semiparametric Monte Carlo simulation evaluated the total (i.e., protein bound plus unbound) area under the plasma concentration-time curve (AUC total ) during the first 24 h of therapy and at 96 h posttherapy for each regimen at the 10th, 50th, and 90th percentiles of TBW and ABW in the derivation cohort. Literature-based values of the 24-h total AUC/MIC ratio (AUC/MIC total ) of ≥50 defined efficacy, and literature-based values of the 72- to 96-h AUC total of ≥100 μg · h/ml defined toxicity. Fifty-two patients contributed 156 PB plasma samples. A two-compartment model with allometric scaling of TBW produced a comparable fit (Akaike information criterion [AIC] = 376.7) to that achieved with linear scaling (AIC = 378). The regimen of a loading dose of 2.5 mg/kg of body weight plus a fixed dose of 100 mg every 12 h had the highest probability of achieving a 24-h AUC/MIC total of ≥50 with the lowest probability of toxicity in all groups at 24 h, aside from those with the lowest 10th percentile of body weight. This is the first study to suggest that a weight-based loading and fixed maintenance (i.e., weight-independent) dosing strategy for polymyxin B may maximize efficacy while balancing toxicity concerns for most patients.
Miglis, C., Rhodes, N. J., Avedissian, S. N., Kubin, C. J., Yin, M. T., Nelson, B. C., Pai, M. P., Scheetz, M. H.
The American Society for Microbiology (ASM)
0066-4804
00664804
1098-6596
10986596
shingle_catch_all_4 Population Pharmacokinetics of Polymyxin B in Acutely Ill Adult Patients [Pharmacology]
Polymyxin B (PB) has reemerged as a common treatment against multidrug-resistant Gram-negative pathogens. However, nephrotoxicity remains a significant dose-limiting side effect, and contemporary pharmacokinetic (PK) data are limited. This study sought to evaluate PB exposure differences in various loading and nonloading strategies according to total body weight (TBW) and adjusted body weight (ABW). Patients treated with PB had plasma samples obtained for clinical care and analyzed using liquid chromatography-tandem mass spectrometry. Compartmental PK models with linear and allometric scaling of TBW were explored. Semiparametric Monte Carlo simulation evaluated the total (i.e., protein bound plus unbound) area under the plasma concentration-time curve (AUC total ) during the first 24 h of therapy and at 96 h posttherapy for each regimen at the 10th, 50th, and 90th percentiles of TBW and ABW in the derivation cohort. Literature-based values of the 24-h total AUC/MIC ratio (AUC/MIC total ) of ≥50 defined efficacy, and literature-based values of the 72- to 96-h AUC total of ≥100 μg · h/ml defined toxicity. Fifty-two patients contributed 156 PB plasma samples. A two-compartment model with allometric scaling of TBW produced a comparable fit (Akaike information criterion [AIC] = 376.7) to that achieved with linear scaling (AIC = 378). The regimen of a loading dose of 2.5 mg/kg of body weight plus a fixed dose of 100 mg every 12 h had the highest probability of achieving a 24-h AUC/MIC total of ≥50 with the lowest probability of toxicity in all groups at 24 h, aside from those with the lowest 10th percentile of body weight. This is the first study to suggest that a weight-based loading and fixed maintenance (i.e., weight-independent) dosing strategy for polymyxin B may maximize efficacy while balancing toxicity concerns for most patients.
Miglis, C., Rhodes, N. J., Avedissian, S. N., Kubin, C. J., Yin, M. T., Nelson, B. C., Pai, M. P., Scheetz, M. H.
The American Society for Microbiology (ASM)
0066-4804
00664804
1098-6596
10986596
shingle_title_1 Population Pharmacokinetics of Polymyxin B in Acutely Ill Adult Patients [Pharmacology]
shingle_title_2 Population Pharmacokinetics of Polymyxin B in Acutely Ill Adult Patients [Pharmacology]
shingle_title_3 Population Pharmacokinetics of Polymyxin B in Acutely Ill Adult Patients [Pharmacology]
shingle_title_4 Population Pharmacokinetics of Polymyxin B in Acutely Ill Adult Patients [Pharmacology]
timestamp 2025-06-30T23:32:58.412Z
titel Population Pharmacokinetics of Polymyxin B in Acutely Ill Adult Patients [Pharmacology]
titel_suche Population Pharmacokinetics of Polymyxin B in Acutely Ill Adult Patients [Pharmacology]
topic W
WW-YZ
uid ipn_articles_6173456