Document Detail


Gentamicin pharmacokinetics and pharmacodynamics during short-daily hemodialysis.
MedLine Citation:
PMID:  22813936     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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 (Cl(dial)) 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 Cl(dial) and interindividual variability terms (IIV) were estimated using NONMEM VII. Influence of patient weight on systemic clearance (Cl(s)) and central volume of distribution (V(c)) and influence of urea removal estimates on Cl(dial) 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 Cl(s) and Cl(dial) were 7.6 and 134 ml/min, respectively. Patient weight was statistically significantly associated with Cl(s) and V(c). Predialysis every-other-day regimens were as effective (C(max) ≥8 mg/l and AUC(48 h) ≥140 mg·h/l) and less toxic (C(min) <2 mg/l and AUC(48 h) <240 mg·h/l) than postdialysis regimens.
CONCLUSIONS: Estimated gentamicin Cl(dial) is higher than previous estimates with thrice-weekly regimens. Predialysis every-other-day dosing may be recommended during SDHD.
Authors:
Brian S Decker; Ahmed N Mohamed; Mary Chambers; Michael A Kraus; Sharon M Moe; Kevin M Sowinski
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Publication Detail:
Type:  Clinical Trial; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2012-07-18
Journal Detail:
Title:  American journal of nephrology     Volume:  36     ISSN:  1421-9670     ISO Abbreviation:  Am. J. Nephrol.     Publication Date:  2012  
Date Detail:
Created Date:  2012-08-27     Completed Date:  2013-01-07     Revised Date:  2014-03-19    
Medline Journal Info:
Nlm Unique ID:  8109361     Medline TA:  Am J Nephrol     Country:  Switzerland    
Other Details:
Languages:  eng     Pagination:  144-50     Citation Subset:  IM    
Copyright Information:
Copyright © 2012 S. Karger AG, Basel.
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MeSH Terms
Descriptor/Qualifier:
Adult
Anti-Bacterial Agents / administration & dosage,  pharmacokinetics*
Bacterial Infections / drug therapy*,  metabolism
Female
Gentamicins / administration & dosage,  pharmacokinetics*
Humans
Infusions, Intravenous
Kidney Failure, Chronic / metabolism,  therapy*
Male
Middle Aged
Models, Biological
Renal Dialysis*
Time Factors
Grant Support
ID/Acronym/Agency:
K23 DK084260/DK/NIDDK NIH HHS; RR025761/RR/NCRR NIH HHS; UL1 TR000006/TR/NCATS NIH HHS
Chemical
Reg. No./Substance:
0/Anti-Bacterial Agents; 0/Gentamicins

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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