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Total plasma protein effect on tacrolimus elimination in kidney transplant patients - Population pharmacokinetic approach

Authorized Users Only
2014
Authors
Golubović, Bojana
Vučićević, Katarina
Radivojević, Dragana
Vezmar-Kovačević, Sandra
Prostran, Milica
Miljković, Branislava
Article (Published version)
Metadata
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Abstract
Data from routine therapeutic drug monitoring of 105 adult kidney transplant recipients were used for population pharmacokinetic analysis which was performed using a non-linear mixed-effects modeling. The effect of demographic and clinical factors on tacrolimus clearance was evaluated. Following the initiation of treatment with tacrolimus, the results of our study indicate a decrease of the drug clearance on day 15, 1 and 6 months after transplantation for 4.4%, 6.3% and 10.92%, respectively. Our model suggests a negative correlation between tacrolimus clearance and haematocrit. According to final model, clearance decreases with increasing of aspartate aminotransferase. Our results demonstrated that CL/F increases with patients' weight. This study reveals incensement for 10.4% in tacrolimus clearance with alteration of patients' minimal measured total protein levels to upper normal range. The findings of this study explore various factors of tacrolimus pharmacokinetic variability and p...oint out a relationship between tacrolimus clearance and total plasma protein. Developed model demonstrates the feasibility of estimation of individual tacrolimus clearance and may allow rational individualization of tacrolimus dosing in kidney transplant patients.

Keywords:
Kidney transplantation / Plasma proteins / Population pharmacokinetics / Tacrolimus / Therapeutic monitoring
Source:
European Journal of Pharmaceutical Sciences, 2014, 52, 34-40
Publisher:
  • Elsevier Science BV, Amsterdam
Funding / projects:
  • Basic and Clinical Pharmacological research of mechanisms of action and drug interactions in nervous and cardiovascular system (RS-175023)

DOI: 10.1016/j.ejps.2013.10.008

ISSN: 0928-0987

PubMed: 24184751

WoS: 000331022100005

Scopus: 2-s2.0-84887585346
[ Google Scholar ]
28
23
URI
https://farfar.pharmacy.bg.ac.rs/handle/123456789/2174
Collections
  • Radovi istraživača / Researchers’ publications
Institution/Community
Pharmacy
TY  - JOUR
AU  - Golubović, Bojana
AU  - Vučićević, Katarina
AU  - Radivojević, Dragana
AU  - Vezmar-Kovačević, Sandra
AU  - Prostran, Milica
AU  - Miljković, Branislava
PY  - 2014
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/2174
AB  - Data from routine therapeutic drug monitoring of 105 adult kidney transplant recipients were used for population pharmacokinetic analysis which was performed using a non-linear mixed-effects modeling. The effect of demographic and clinical factors on tacrolimus clearance was evaluated. Following the initiation of treatment with tacrolimus, the results of our study indicate a decrease of the drug clearance on day 15, 1 and 6 months after transplantation for 4.4%, 6.3% and 10.92%, respectively. Our model suggests a negative correlation between tacrolimus clearance and haematocrit. According to final model, clearance decreases with increasing of aspartate aminotransferase. Our results demonstrated that CL/F increases with patients' weight. This study reveals incensement for 10.4% in tacrolimus clearance with alteration of patients' minimal measured total protein levels to upper normal range. The findings of this study explore various factors of tacrolimus pharmacokinetic variability and point out a relationship between tacrolimus clearance and total plasma protein. Developed model demonstrates the feasibility of estimation of individual tacrolimus clearance and may allow rational individualization of tacrolimus dosing in kidney transplant patients.
PB  - Elsevier Science BV, Amsterdam
T2  - European Journal of Pharmaceutical Sciences
T1  - Total plasma protein effect on tacrolimus elimination in kidney transplant patients - Population pharmacokinetic approach
VL  - 52
SP  - 34
EP  - 40
DO  - 10.1016/j.ejps.2013.10.008
ER  - 
@article{
author = "Golubović, Bojana and Vučićević, Katarina and Radivojević, Dragana and Vezmar-Kovačević, Sandra and Prostran, Milica and Miljković, Branislava",
year = "2014",
abstract = "Data from routine therapeutic drug monitoring of 105 adult kidney transplant recipients were used for population pharmacokinetic analysis which was performed using a non-linear mixed-effects modeling. The effect of demographic and clinical factors on tacrolimus clearance was evaluated. Following the initiation of treatment with tacrolimus, the results of our study indicate a decrease of the drug clearance on day 15, 1 and 6 months after transplantation for 4.4%, 6.3% and 10.92%, respectively. Our model suggests a negative correlation between tacrolimus clearance and haematocrit. According to final model, clearance decreases with increasing of aspartate aminotransferase. Our results demonstrated that CL/F increases with patients' weight. This study reveals incensement for 10.4% in tacrolimus clearance with alteration of patients' minimal measured total protein levels to upper normal range. The findings of this study explore various factors of tacrolimus pharmacokinetic variability and point out a relationship between tacrolimus clearance and total plasma protein. Developed model demonstrates the feasibility of estimation of individual tacrolimus clearance and may allow rational individualization of tacrolimus dosing in kidney transplant patients.",
publisher = "Elsevier Science BV, Amsterdam",
journal = "European Journal of Pharmaceutical Sciences",
title = "Total plasma protein effect on tacrolimus elimination in kidney transplant patients - Population pharmacokinetic approach",
volume = "52",
pages = "34-40",
doi = "10.1016/j.ejps.2013.10.008"
}
Golubović, B., Vučićević, K., Radivojević, D., Vezmar-Kovačević, S., Prostran, M.,& Miljković, B.. (2014). Total plasma protein effect on tacrolimus elimination in kidney transplant patients - Population pharmacokinetic approach. in European Journal of Pharmaceutical Sciences
Elsevier Science BV, Amsterdam., 52, 34-40.
https://doi.org/10.1016/j.ejps.2013.10.008
Golubović B, Vučićević K, Radivojević D, Vezmar-Kovačević S, Prostran M, Miljković B. Total plasma protein effect on tacrolimus elimination in kidney transplant patients - Population pharmacokinetic approach. in European Journal of Pharmaceutical Sciences. 2014;52:34-40.
doi:10.1016/j.ejps.2013.10.008 .
Golubović, Bojana, Vučićević, Katarina, Radivojević, Dragana, Vezmar-Kovačević, Sandra, Prostran, Milica, Miljković, Branislava, "Total plasma protein effect on tacrolimus elimination in kidney transplant patients - Population pharmacokinetic approach" in European Journal of Pharmaceutical Sciences, 52 (2014):34-40,
https://doi.org/10.1016/j.ejps.2013.10.008 . .

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