Polymyxin B Pharmacokinetics in Adult Cystic Fibrosis Patients

Sean N. Avedissian, Cristina Miglis, Christine J. Kubin, Nathaniel J. Rhodes, Michael T. Yin, Serge Cremers, Michelle Prickett, Marc H. Scheetz*

*Corresponding author for this work

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Objectives: Polymyxin B pharmacokinetics (PK) in adults with cystic fibrosis (CF) are not well described. The goals of this pilot study were to identify a PK model for patients with CF receiving polymyxin B with exploration of covariate relationships of the PK parameters, to compare polymyxin B PK parameters in adults without CF, and to probe exposures associated with different dosing schemes through simulation. Methods: Adult patients with CF treated with polymyxin B at New York-Presbyterian Hospital had PK samples measured by liquid chromatography–mass spectrometry (MS)/MS. Multiple PK models were fit utilizing Pmetrics for R. Model covariates considered included: age, total body weight, creatinine clearance, albumin, and body mass index. PK parameters in CF patients were compared with PK parameters for 53 adults without CF who were receiving polymyxin B from the same institution. Simulations with target exposure (area under the curve)/minimum inhibitory concentration (MIC) of 20 mg*L/h were conducted for different dosing schemes and MIC ranges. Main Results: Nine patients with CF received between 58 and 240 mg of polymyxin B (median 1.47 mg/kg/dose [IQR (1.43–1.65)]). A two-compartment model adjusting polymyxin B clearance for patient CrCl was better than a standard two-compartment model (p=0.004) in CF patients. When compared to PK parameters for patients without CF, PK parameters of polymyxin B in CF were similar (p>0.05). Simulations for plasma concentrations showed all regimens performed adequately at MICs between 0.03125 and 0.125 mg/L but not at increasing MICs of 1 and 2 mg/L. Conclusions: In this pilot study of polymyxin B PK in adults with CF, the PK parameters of polymyxin B were mostly similar to adults without CF. We observed a potential association between CrCl and polymyxin B clearance, which stands in contrast to the general adult population. However, this observation requires further study. Additional studies focusing on optimal and safe polymyxin B dosing in CF are needed.

Original languageEnglish (US)
Pages (from-to)730-738
Number of pages9
JournalPharmacotherapy
Volume38
Issue number7
DOIs
StatePublished - Jul 1 2018

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Polymyxin B
Cystic Fibrosis
Pharmacokinetics
Microbial Sensitivity Tests
Area Under Curve
Albumins
Creatinine
Spectrum Analysis

Keywords

  • cystic fibrosis
  • pharmacokinetics
  • polymyxin B

ASJC Scopus subject areas

  • Pharmacology (medical)

Cite this

Avedissian, S. N., Miglis, C., Kubin, C. J., Rhodes, N. J., Yin, M. T., Cremers, S., ... Scheetz, M. H. (2018). Polymyxin B Pharmacokinetics in Adult Cystic Fibrosis Patients. Pharmacotherapy, 38(7), 730-738. https://doi.org/10.1002/phar.2129
Avedissian, Sean N. ; Miglis, Cristina ; Kubin, Christine J. ; Rhodes, Nathaniel J. ; Yin, Michael T. ; Cremers, Serge ; Prickett, Michelle ; Scheetz, Marc H. / Polymyxin B Pharmacokinetics in Adult Cystic Fibrosis Patients. In: Pharmacotherapy. 2018 ; Vol. 38, No. 7. pp. 730-738.
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abstract = "Objectives: Polymyxin B pharmacokinetics (PK) in adults with cystic fibrosis (CF) are not well described. The goals of this pilot study were to identify a PK model for patients with CF receiving polymyxin B with exploration of covariate relationships of the PK parameters, to compare polymyxin B PK parameters in adults without CF, and to probe exposures associated with different dosing schemes through simulation. Methods: Adult patients with CF treated with polymyxin B at New York-Presbyterian Hospital had PK samples measured by liquid chromatography–mass spectrometry (MS)/MS. Multiple PK models were fit utilizing Pmetrics for R. Model covariates considered included: age, total body weight, creatinine clearance, albumin, and body mass index. PK parameters in CF patients were compared with PK parameters for 53 adults without CF who were receiving polymyxin B from the same institution. Simulations with target exposure (area under the curve)/minimum inhibitory concentration (MIC) of 20 mg*L/h were conducted for different dosing schemes and MIC ranges. Main Results: Nine patients with CF received between 58 and 240 mg of polymyxin B (median 1.47 mg/kg/dose [IQR (1.43–1.65)]). A two-compartment model adjusting polymyxin B clearance for patient CrCl was better than a standard two-compartment model (p=0.004) in CF patients. When compared to PK parameters for patients without CF, PK parameters of polymyxin B in CF were similar (p>0.05). Simulations for plasma concentrations showed all regimens performed adequately at MICs between 0.03125 and 0.125 mg/L but not at increasing MICs of 1 and 2 mg/L. Conclusions: In this pilot study of polymyxin B PK in adults with CF, the PK parameters of polymyxin B were mostly similar to adults without CF. We observed a potential association between CrCl and polymyxin B clearance, which stands in contrast to the general adult population. However, this observation requires further study. Additional studies focusing on optimal and safe polymyxin B dosing in CF are needed.",
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Avedissian, SN, Miglis, C, Kubin, CJ, Rhodes, NJ, Yin, MT, Cremers, S, Prickett, M & Scheetz, MH 2018, 'Polymyxin B Pharmacokinetics in Adult Cystic Fibrosis Patients', Pharmacotherapy, vol. 38, no. 7, pp. 730-738. https://doi.org/10.1002/phar.2129

Polymyxin B Pharmacokinetics in Adult Cystic Fibrosis Patients. / Avedissian, Sean N.; Miglis, Cristina; Kubin, Christine J.; Rhodes, Nathaniel J.; Yin, Michael T.; Cremers, Serge; Prickett, Michelle; Scheetz, Marc H.

In: Pharmacotherapy, Vol. 38, No. 7, 01.07.2018, p. 730-738.

Research output: Contribution to journalArticle

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T1 - Polymyxin B Pharmacokinetics in Adult Cystic Fibrosis Patients

AU - Avedissian, Sean N.

AU - Miglis, Cristina

AU - Kubin, Christine J.

AU - Rhodes, Nathaniel J.

AU - Yin, Michael T.

AU - Cremers, Serge

AU - Prickett, Michelle

AU - Scheetz, Marc H.

PY - 2018/7/1

Y1 - 2018/7/1

N2 - Objectives: Polymyxin B pharmacokinetics (PK) in adults with cystic fibrosis (CF) are not well described. The goals of this pilot study were to identify a PK model for patients with CF receiving polymyxin B with exploration of covariate relationships of the PK parameters, to compare polymyxin B PK parameters in adults without CF, and to probe exposures associated with different dosing schemes through simulation. Methods: Adult patients with CF treated with polymyxin B at New York-Presbyterian Hospital had PK samples measured by liquid chromatography–mass spectrometry (MS)/MS. Multiple PK models were fit utilizing Pmetrics for R. Model covariates considered included: age, total body weight, creatinine clearance, albumin, and body mass index. PK parameters in CF patients were compared with PK parameters for 53 adults without CF who were receiving polymyxin B from the same institution. Simulations with target exposure (area under the curve)/minimum inhibitory concentration (MIC) of 20 mg*L/h were conducted for different dosing schemes and MIC ranges. Main Results: Nine patients with CF received between 58 and 240 mg of polymyxin B (median 1.47 mg/kg/dose [IQR (1.43–1.65)]). A two-compartment model adjusting polymyxin B clearance for patient CrCl was better than a standard two-compartment model (p=0.004) in CF patients. When compared to PK parameters for patients without CF, PK parameters of polymyxin B in CF were similar (p>0.05). Simulations for plasma concentrations showed all regimens performed adequately at MICs between 0.03125 and 0.125 mg/L but not at increasing MICs of 1 and 2 mg/L. Conclusions: In this pilot study of polymyxin B PK in adults with CF, the PK parameters of polymyxin B were mostly similar to adults without CF. We observed a potential association between CrCl and polymyxin B clearance, which stands in contrast to the general adult population. However, this observation requires further study. Additional studies focusing on optimal and safe polymyxin B dosing in CF are needed.

AB - Objectives: Polymyxin B pharmacokinetics (PK) in adults with cystic fibrosis (CF) are not well described. The goals of this pilot study were to identify a PK model for patients with CF receiving polymyxin B with exploration of covariate relationships of the PK parameters, to compare polymyxin B PK parameters in adults without CF, and to probe exposures associated with different dosing schemes through simulation. Methods: Adult patients with CF treated with polymyxin B at New York-Presbyterian Hospital had PK samples measured by liquid chromatography–mass spectrometry (MS)/MS. Multiple PK models were fit utilizing Pmetrics for R. Model covariates considered included: age, total body weight, creatinine clearance, albumin, and body mass index. PK parameters in CF patients were compared with PK parameters for 53 adults without CF who were receiving polymyxin B from the same institution. Simulations with target exposure (area under the curve)/minimum inhibitory concentration (MIC) of 20 mg*L/h were conducted for different dosing schemes and MIC ranges. Main Results: Nine patients with CF received between 58 and 240 mg of polymyxin B (median 1.47 mg/kg/dose [IQR (1.43–1.65)]). A two-compartment model adjusting polymyxin B clearance for patient CrCl was better than a standard two-compartment model (p=0.004) in CF patients. When compared to PK parameters for patients without CF, PK parameters of polymyxin B in CF were similar (p>0.05). Simulations for plasma concentrations showed all regimens performed adequately at MICs between 0.03125 and 0.125 mg/L but not at increasing MICs of 1 and 2 mg/L. Conclusions: In this pilot study of polymyxin B PK in adults with CF, the PK parameters of polymyxin B were mostly similar to adults without CF. We observed a potential association between CrCl and polymyxin B clearance, which stands in contrast to the general adult population. However, this observation requires further study. Additional studies focusing on optimal and safe polymyxin B dosing in CF are needed.

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KW - pharmacokinetics

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Avedissian SN, Miglis C, Kubin CJ, Rhodes NJ, Yin MT, Cremers S et al. Polymyxin B Pharmacokinetics in Adult Cystic Fibrosis Patients. Pharmacotherapy. 2018 Jul 1;38(7):730-738. https://doi.org/10.1002/phar.2129