Gentamicin pharmacokinetics and pharmacodynamics during short-daily hemodialysis

Brian Decker, Ahmed N. Mohamed, Mary Chambers, Michael Kraus, Sharon Moe, Kevin M. Sowinski

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Background/Aims: Gentamicin pharmacokinetics have not been described in patients undergoing short-daily hemodialysis (SDHD). The aim of this study is to describe gentamicin pharmacokinetics and dialytic clearance (Cldial) in SDHD patients and simulate gentamicin exposure after six dosing regimens to help guide future dosing. Methods: Six anuric patients undergoing SDHD were enrolled. Patients received intravenous infusion of 2 mg/kg gentamicin on day 1 after the first HD session followed by HD sessions on days 2, 3, and 4. Blood samples for determination of gentamicin concentrations were serially collected. Gentamicin pharmacokinetic parameters and Cldial and interindividual variability terms (IIV) were estimated using NONMEM VII. Influence of patient weight on systemic clearance (Cls) and central volume of distribution (Vc) and influence of urea removal estimates on Cldial were assessed. The model was used to simulate gentamicin concentrations after six dosing regimens including pre- and postdialysis as well as daily and every-other-day dosing. Results: A two-compartment model with first-order elimination from central compartment described gentamicin pharmacokinetics. Population estimates for Cls and Cldial were 7.6 and 134 ml/min, respectively. Patient weight was statistically significantly associated with Cls and Vc. Predialysis every-other-day regimens were as effective (Cmax ≥8 mg/l and AUC48 h ≥140 mg·h/l) and less toxic (Cmin <2 mg/l and AUC48 h <240 mg·h/l) than postdialysis regimens. Conclusions: Estimated gentamicin Cldial is higher than previous estimates with thrice-weekly regimens. Predialysis every-other-day dosing may be recommended during SDHD.

Original languageEnglish
Pages (from-to)144-150
Number of pages7
JournalAmerican Journal of Nephrology
Volume36
Issue number2
DOIs
StatePublished - Aug 2012

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Gentamicins
Renal Dialysis
Pharmacokinetics
Weights and Measures
Poisons
Intravenous Infusions
Urea
Population

Keywords

  • Gentamicin
  • Hemodialysis
  • Pharmacokinetics
  • Renal failure

ASJC Scopus subject areas

  • Nephrology

Cite this

Gentamicin pharmacokinetics and pharmacodynamics during short-daily hemodialysis. / Decker, Brian; Mohamed, Ahmed N.; Chambers, Mary; Kraus, Michael; Moe, Sharon; Sowinski, Kevin M.

In: American Journal of Nephrology, Vol. 36, No. 2, 08.2012, p. 144-150.

Research output: Contribution to journalArticle

Decker, Brian ; Mohamed, Ahmed N. ; Chambers, Mary ; Kraus, Michael ; Moe, Sharon ; Sowinski, Kevin M. / Gentamicin pharmacokinetics and pharmacodynamics during short-daily hemodialysis. In: American Journal of Nephrology. 2012 ; Vol. 36, No. 2. pp. 144-150.
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N2 - Background/Aims: Gentamicin pharmacokinetics have not been described in patients undergoing short-daily hemodialysis (SDHD). The aim of this study is to describe gentamicin pharmacokinetics and dialytic clearance (Cldial) in SDHD patients and simulate gentamicin exposure after six dosing regimens to help guide future dosing. Methods: Six anuric patients undergoing SDHD were enrolled. Patients received intravenous infusion of 2 mg/kg gentamicin on day 1 after the first HD session followed by HD sessions on days 2, 3, and 4. Blood samples for determination of gentamicin concentrations were serially collected. Gentamicin pharmacokinetic parameters and Cldial and interindividual variability terms (IIV) were estimated using NONMEM VII. Influence of patient weight on systemic clearance (Cls) and central volume of distribution (Vc) and influence of urea removal estimates on Cldial were assessed. The model was used to simulate gentamicin concentrations after six dosing regimens including pre- and postdialysis as well as daily and every-other-day dosing. Results: A two-compartment model with first-order elimination from central compartment described gentamicin pharmacokinetics. Population estimates for Cls and Cldial were 7.6 and 134 ml/min, respectively. Patient weight was statistically significantly associated with Cls and Vc. Predialysis every-other-day regimens were as effective (Cmax ≥8 mg/l and AUC48 h ≥140 mg·h/l) and less toxic (Cmin <2 mg/l and AUC48 h <240 mg·h/l) than postdialysis regimens. Conclusions: Estimated gentamicin Cldial is higher than previous estimates with thrice-weekly regimens. Predialysis every-other-day dosing may be recommended during SDHD.

AB - Background/Aims: Gentamicin pharmacokinetics have not been described in patients undergoing short-daily hemodialysis (SDHD). The aim of this study is to describe gentamicin pharmacokinetics and dialytic clearance (Cldial) in SDHD patients and simulate gentamicin exposure after six dosing regimens to help guide future dosing. Methods: Six anuric patients undergoing SDHD were enrolled. Patients received intravenous infusion of 2 mg/kg gentamicin on day 1 after the first HD session followed by HD sessions on days 2, 3, and 4. Blood samples for determination of gentamicin concentrations were serially collected. Gentamicin pharmacokinetic parameters and Cldial and interindividual variability terms (IIV) were estimated using NONMEM VII. Influence of patient weight on systemic clearance (Cls) and central volume of distribution (Vc) and influence of urea removal estimates on Cldial were assessed. The model was used to simulate gentamicin concentrations after six dosing regimens including pre- and postdialysis as well as daily and every-other-day dosing. Results: A two-compartment model with first-order elimination from central compartment described gentamicin pharmacokinetics. Population estimates for Cls and Cldial were 7.6 and 134 ml/min, respectively. Patient weight was statistically significantly associated with Cls and Vc. Predialysis every-other-day regimens were as effective (Cmax ≥8 mg/l and AUC48 h ≥140 mg·h/l) and less toxic (Cmin <2 mg/l and AUC48 h <240 mg·h/l) than postdialysis regimens. Conclusions: Estimated gentamicin Cldial is higher than previous estimates with thrice-weekly regimens. Predialysis every-other-day dosing may be recommended during SDHD.

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