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

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2014
Authors
Golubović, Bojana
Vučićević, Katarina
Radivojević, Dragana
Vezmar-Kovačević, Sandra
Prostran, Milica
Miljković, Branislava
Article (Published version)
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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
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
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URI
http://farfar.pharmacy.bg.ac.rs/handle/123456789/2174
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Pharmacy

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