Population Pharmacokinetics of Polymyxin B in Obese Patients for Resistant Gram-Negative Infections
Polymyxin B is an effective but potentially nephrotoxic antibiotic that is commonly used to treat resistant Gram-negative infections. As a weight-based dosing drug, obese patients may be at a high risk of nephrotoxicity. However, the pharmacokinetics and dosing recommendations for this population ar...
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Frontiers Media S.A.
2021
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oai:doaj.org-article:54b12a7c1f4344fabe5c1431ad7642012021-11-22T06:42:46ZPopulation Pharmacokinetics of Polymyxin B in Obese Patients for Resistant Gram-Negative Infections1663-981210.3389/fphar.2021.754844https://doaj.org/article/54b12a7c1f4344fabe5c1431ad7642012021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fphar.2021.754844/fullhttps://doaj.org/toc/1663-9812Polymyxin B is an effective but potentially nephrotoxic antibiotic that is commonly used to treat resistant Gram-negative infections. As a weight-based dosing drug, obese patients may be at a high risk of nephrotoxicity. However, the pharmacokinetics and dosing recommendations for this population are currently lacking. This study aimed to describe the polymyxin B population pharmacokinetics and to evaluate pharmacokinetic/pharmacodynamics (PK/PD) target attainment for obese patients. This study included 26 patients (body mass index, BMI >30) who received polymyxin B for ≥3 days. The total body weight (TBW) ranged from 75 to 125 kg, and the BMI ranged from 30.04 to 40.35. A two-compartment model adequately described the data using Phoenix NLME software. Monte Carlo simulation was used to assess polymyxin B exposure and the probability of target attainment (PTA). As a result, body weight had no significant effect on polymyxin B pharmacokinetics. According to model-based simulation, adjusted body weight (ABW)-based regimens had a high probability of achieving optimal exposure with minimal toxicity risk by comparing TBW and ideal body weight (IBW)-based regimens. The fixed dose of 125 mg or 150 mg q12h had a high toxicity risk. PTA results showed that TBW, IBW, and ABW-based regimens had similar PTA values. Therefore, for obese patients, ABW-based regimens but with a daily dose <250 mg have a high likelihood of achieving an AUCss,24h of 50–100 mg h/L and attaining PK/PD targets with the MIC ≤0.5 mg/L.Peile WangPeile WangQiwen ZhangQiwen ZhangMin FengTongwen SunJing YangJing YangXiaojian ZhangXiaojian ZhangFrontiers Media S.A.articlepolymyxin Bobesitypopulation pharmacokineticsMonte Carlo simulationadjusted body weightTherapeutics. PharmacologyRM1-950ENFrontiers in Pharmacology, Vol 12 (2021) |
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polymyxin B obesity population pharmacokinetics Monte Carlo simulation adjusted body weight Therapeutics. Pharmacology RM1-950 |
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polymyxin B obesity population pharmacokinetics Monte Carlo simulation adjusted body weight Therapeutics. Pharmacology RM1-950 Peile Wang Peile Wang Qiwen Zhang Qiwen Zhang Min Feng Tongwen Sun Jing Yang Jing Yang Xiaojian Zhang Xiaojian Zhang Population Pharmacokinetics of Polymyxin B in Obese Patients for Resistant Gram-Negative Infections |
| description |
Polymyxin B is an effective but potentially nephrotoxic antibiotic that is commonly used to treat resistant Gram-negative infections. As a weight-based dosing drug, obese patients may be at a high risk of nephrotoxicity. However, the pharmacokinetics and dosing recommendations for this population are currently lacking. This study aimed to describe the polymyxin B population pharmacokinetics and to evaluate pharmacokinetic/pharmacodynamics (PK/PD) target attainment for obese patients. This study included 26 patients (body mass index, BMI >30) who received polymyxin B for ≥3 days. The total body weight (TBW) ranged from 75 to 125 kg, and the BMI ranged from 30.04 to 40.35. A two-compartment model adequately described the data using Phoenix NLME software. Monte Carlo simulation was used to assess polymyxin B exposure and the probability of target attainment (PTA). As a result, body weight had no significant effect on polymyxin B pharmacokinetics. According to model-based simulation, adjusted body weight (ABW)-based regimens had a high probability of achieving optimal exposure with minimal toxicity risk by comparing TBW and ideal body weight (IBW)-based regimens. The fixed dose of 125 mg or 150 mg q12h had a high toxicity risk. PTA results showed that TBW, IBW, and ABW-based regimens had similar PTA values. Therefore, for obese patients, ABW-based regimens but with a daily dose <250 mg have a high likelihood of achieving an AUCss,24h of 50–100 mg h/L and attaining PK/PD targets with the MIC ≤0.5 mg/L. |
| format |
article |
| author |
Peile Wang Peile Wang Qiwen Zhang Qiwen Zhang Min Feng Tongwen Sun Jing Yang Jing Yang Xiaojian Zhang Xiaojian Zhang |
| author_facet |
Peile Wang Peile Wang Qiwen Zhang Qiwen Zhang Min Feng Tongwen Sun Jing Yang Jing Yang Xiaojian Zhang Xiaojian Zhang |
| author_sort |
Peile Wang |
| title |
Population Pharmacokinetics of Polymyxin B in Obese Patients for Resistant Gram-Negative Infections |
| title_short |
Population Pharmacokinetics of Polymyxin B in Obese Patients for Resistant Gram-Negative Infections |
| title_full |
Population Pharmacokinetics of Polymyxin B in Obese Patients for Resistant Gram-Negative Infections |
| title_fullStr |
Population Pharmacokinetics of Polymyxin B in Obese Patients for Resistant Gram-Negative Infections |
| title_full_unstemmed |
Population Pharmacokinetics of Polymyxin B in Obese Patients for Resistant Gram-Negative Infections |
| title_sort |
population pharmacokinetics of polymyxin b in obese patients for resistant gram-negative infections |
| publisher |
Frontiers Media S.A. |
| publishDate |
2021 |
| url |
https://doaj.org/article/54b12a7c1f4344fabe5c1431ad764201 |
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