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...
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2021-11-01
|
| Series: | Frontiers in Pharmacology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2021.754844/full |
| _version_ | 1818398307343400960 |
|---|---|
| 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 |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-14T07:02:42Z |
| format | Article |
| id | doaj.art-54b12a7c1f4344fabe5c1431ad764201 |
| institution | Directory Open Access Journal |
| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-12-14T07:02:42Z |
| publishDate | 2021-11-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj.art-54b12a7c1f4344fabe5c1431ad7642012022-12-21T23:12:21ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122021-11-011210.3389/fphar.2021.754844754844Population Pharmacokinetics of Polymyxin B in Obese Patients for Resistant Gram-Negative InfectionsPeile Wang0Peile Wang1Qiwen Zhang2Qiwen Zhang3Min Feng4Tongwen Sun5Jing Yang6Jing Yang7Xiaojian Zhang8Xiaojian Zhang9Department of Pharmacy, First Affiliated Hospital of Zhengzhou University, Zhengzhou, ChinaHenan Key Laboratory of Precision Clinical Pharmacy, Zhengzhou University, Zhengzhou, ChinaDepartment of Pharmacy, First Affiliated Hospital of Zhengzhou University, Zhengzhou, ChinaHenan Key Laboratory of Precision Clinical Pharmacy, Zhengzhou University, Zhengzhou, ChinaDepartment of ICU, First Affiliated Hospital of Zhengzhou University, Zhengzhou, ChinaDepartment of General ICU, First Affiliated Hospital of Zhengzhou University, Zhengzhou, ChinaDepartment of Pharmacy, First Affiliated Hospital of Zhengzhou University, Zhengzhou, ChinaHenan Key Laboratory of Precision Clinical Pharmacy, Zhengzhou University, Zhengzhou, ChinaDepartment of Pharmacy, First Affiliated Hospital of Zhengzhou University, Zhengzhou, ChinaHenan Key Laboratory of Precision Clinical Pharmacy, Zhengzhou University, Zhengzhou, ChinaPolymyxin 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.https://www.frontiersin.org/articles/10.3389/fphar.2021.754844/fullpolymyxin Bobesitypopulation pharmacokineticsMonte Carlo simulationadjusted body weight |
| spellingShingle | 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 Frontiers in Pharmacology polymyxin B obesity population pharmacokinetics Monte Carlo simulation adjusted body weight |
| title | 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_short | 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 |
| topic | polymyxin B obesity population pharmacokinetics Monte Carlo simulation adjusted body weight |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2021.754844/full |
| work_keys_str_mv | AT peilewang populationpharmacokineticsofpolymyxinbinobesepatientsforresistantgramnegativeinfections AT peilewang populationpharmacokineticsofpolymyxinbinobesepatientsforresistantgramnegativeinfections AT qiwenzhang populationpharmacokineticsofpolymyxinbinobesepatientsforresistantgramnegativeinfections AT qiwenzhang populationpharmacokineticsofpolymyxinbinobesepatientsforresistantgramnegativeinfections AT minfeng populationpharmacokineticsofpolymyxinbinobesepatientsforresistantgramnegativeinfections AT tongwensun populationpharmacokineticsofpolymyxinbinobesepatientsforresistantgramnegativeinfections AT jingyang populationpharmacokineticsofpolymyxinbinobesepatientsforresistantgramnegativeinfections AT jingyang populationpharmacokineticsofpolymyxinbinobesepatientsforresistantgramnegativeinfections AT xiaojianzhang populationpharmacokineticsofpolymyxinbinobesepatientsforresistantgramnegativeinfections AT xiaojianzhang populationpharmacokineticsofpolymyxinbinobesepatientsforresistantgramnegativeinfections |