The Pharmacokinetics of Recombinant Human Erythropoietin in Balkan Endemic Nephropathy Patients
2013
Authors
Lezaić, VišnjaPetković, Nenad
Marić, Ivko
Miljković, Branislava
Vučićević, Katarina
Simić-Ogrizović, Sanja
Pejović, Vesna
Đukanović, Ljubica
Article (Published version)
Metadata
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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 / PharmacokineticsSource:
Nefrologia, 2013, 33, 4, 478-485Publisher:
- Soc Espanola Nefrologia Dr Rafael Matesanz, Madrid
Funding / projects:
- Biomarkers for kidney diseases: diagnostic and prognostic significance (RS-MESTD-Basic Research (BR or ON)-175089)
DOI: 10.3265/Nefrologia.pre2013.Apr.11800
ISSN: 0211-6995
PubMed: 23897179
WoS: 000330094500005
Scopus: 2-s2.0-84883008692
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Institution/Community
PharmacyTY - JOUR AU - Lezaić, Višnja AU - Petković, Nenad AU - Marić, Ivko AU - Miljković, Branislava AU - Vučićević, Katarina AU - Simić-Ogrizović, Sanja AU - Pejović, Vesna AU - Đukanović, Ljubica PY - 2013 UR - https://farfar.pharmacy.bg.ac.rs/handle/123456789/1882 AB - 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 +/- 0.011 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. PB - Soc Espanola Nefrologia Dr Rafael Matesanz, Madrid T2 - Nefrologia T1 - The Pharmacokinetics of Recombinant Human Erythropoietin in Balkan Endemic Nephropathy Patients VL - 33 IS - 4 SP - 478 EP - 485 DO - 10.3265/Nefrologia.pre2013.Apr.11800 ER -
@article{ author = "Lezaić, Višnja and Petković, Nenad and Marić, Ivko and Miljković, Branislava and Vučićević, Katarina and Simić-Ogrizović, Sanja and Pejović, Vesna and Đukanović, Ljubica", year = "2013", 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 +/- 0.011 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.", publisher = "Soc Espanola Nefrologia Dr Rafael Matesanz, Madrid", journal = "Nefrologia", title = "The Pharmacokinetics of Recombinant Human Erythropoietin in Balkan Endemic Nephropathy Patients", volume = "33", number = "4", pages = "478-485", doi = "10.3265/Nefrologia.pre2013.Apr.11800" }
Lezaić, V., Petković, N., Marić, I., Miljković, B., Vučićević, K., Simić-Ogrizović, S., Pejović, V.,& Đukanović, L.. (2013). The Pharmacokinetics of Recombinant Human Erythropoietin in Balkan Endemic Nephropathy Patients. in Nefrologia Soc Espanola Nefrologia Dr Rafael Matesanz, Madrid., 33(4), 478-485. https://doi.org/10.3265/Nefrologia.pre2013.Apr.11800
Lezaić V, Petković N, Marić I, Miljković B, Vučićević K, Simić-Ogrizović S, Pejović V, Đukanović L. The Pharmacokinetics of Recombinant Human Erythropoietin in Balkan Endemic Nephropathy Patients. in Nefrologia. 2013;33(4):478-485. doi:10.3265/Nefrologia.pre2013.Apr.11800 .
Lezaić, Višnja, Petković, Nenad, Marić, Ivko, Miljković, Branislava, Vučićević, Katarina, Simić-Ogrizović, Sanja, Pejović, Vesna, Đukanović, Ljubica, "The Pharmacokinetics of Recombinant Human Erythropoietin in Balkan Endemic Nephropathy Patients" in Nefrologia, 33, no. 4 (2013):478-485, https://doi.org/10.3265/Nefrologia.pre2013.Apr.11800 . .