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The Pharmacokinetics of Recombinant Human Erythropoietin in Balkan Endemic Nephropathy Patients

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2013
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Authors
Lezaić, Višnja
Petković, Nenad
Marić, Ivko
Miljković, Branislava
Vučićević, Katarina
Simić-Ogrizović, Sanja
Pejović, Vesna
Đukanović, Ljubica
Article (Published version)
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Abstract
Background: Balkan endemic nephropathy (BEN) hemodialysis patients require a higher dose of recombinant human erythropoietin for maintaining target hemoglobin level than patients with other kidney diseases. Objectives: Comparison of the pharmacokinetics of beta-erythropoietin given subcutaneously to hemodialysis patients with BEN or other kidney diseases (non-BEN). Methods: Recombinant human erythropoietin (75U/kg) was administered subcutaneously to 10 BEN and 14 non-BEN hemodialysis patients. The predose plasma level of erythropoietin (Epo) was subtracted from all postdose levels. The relevant pharmacokinetic parameters were calculated after noncompartmental pharmacokinetic analysis using Kinetica software (Thermo Scientific, ver.5.0). Results: Although basal plasma Epo concentration was similar in BEN (20.1 +/- 10.3U/L) and non-BEN (15.1 +/- 8.1U/L; p=.1964) patients, there were significant differences between the groups for elimination rate constant (0.016 +/- 0.006 vs 0.026 +/- 0.0...11 hr(-1); p=.020) and elimination half-life (50.24 +/- 19.12 vs 33.79 +/- 18.91 hr, p=.048). These differences remained significant after adjustment for patient characteristics (age, sex, hennodialysis duration, ferritin, PTH and ACEI use). No significant differences between groups were found in maximal Epo concentration, time to maximum Epo concentration, area under the curve from time of dosing extrapolated to infinity, clearance, mean residence time of Epo between groups both before and after adjustment. Conclusion: Pharmacokinetic analysis of beta-erythropoietin detected a significantly longer elimination half-life in BEN than in non BEN patients. This finding needs to be confirmed in a well-controlled study with a larger sample size.

Keywords:
Balkan endemic nephropathy / Human recombinant erythropoietin / Pharmacokinetics
Source:
Nefrologia, 2013, 33, 4, 478-485
Publisher:
  • Soc Espanola Nefrologia Dr Rafael Matesanz, Madrid
Projects:
  • Biomarkers for kidney diseases: diagnostic and prognostic significance (RS-175089)

DOI: 10.3265/Nefrologia.pre2013.Apr.11800

ISSN: 0211-6995

PubMed: 23897179

WoS: 000330094500005

Scopus: 2-s2.0-84883008692
[ Google Scholar ]
URI
http://farfar.pharmacy.bg.ac.rs/handle/123456789/1882
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  • Radovi istraživača / Researchers’ publications
Institution
Pharmacy

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