The kidneys play an important role in the clearance of rFVIIa in rats

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The kidneys play an important role in the clearance of rFVIIa in rats. / Vestergaard, Bill; Appa, Rupa S.; Lykkesfeldt, Jens; Agersø, Henrik.

In: Thrombosis Research, Vol. 133, No. 6, 2014, p. 1124-1129.

Research output: Contribution to journalJournal articleResearchpeer-review

Harvard

Vestergaard, B, Appa, RS, Lykkesfeldt, J & Agersø, H 2014, 'The kidneys play an important role in the clearance of rFVIIa in rats', Thrombosis Research, vol. 133, no. 6, pp. 1124-1129. https://doi.org/10.1016/j.thromres.2014.03.034

APA

Vestergaard, B., Appa, R. S., Lykkesfeldt, J., & Agersø, H. (2014). The kidneys play an important role in the clearance of rFVIIa in rats. Thrombosis Research, 133(6), 1124-1129. https://doi.org/10.1016/j.thromres.2014.03.034

Vancouver

Vestergaard B, Appa RS, Lykkesfeldt J, Agersø H. The kidneys play an important role in the clearance of rFVIIa in rats. Thrombosis Research. 2014;133(6):1124-1129. https://doi.org/10.1016/j.thromres.2014.03.034

Author

Vestergaard, Bill ; Appa, Rupa S. ; Lykkesfeldt, Jens ; Agersø, Henrik. / The kidneys play an important role in the clearance of rFVIIa in rats. In: Thrombosis Research. 2014 ; Vol. 133, No. 6. pp. 1124-1129.

Bibtex

@article{0ac3de9e06084396ad6e785f7e71bdad,
title = "The kidneys play an important role in the clearance of rFVIIa in rats",
abstract = "INTRODUCTION: Previous distribution and histological studies have indicated that the kidneys and renal proximal tubular cells play a role in clearance of rFVIIa. However, the relative importance of the kidneys in clearance of rFVIIa has not previously been addressed. The objective of the present study was to evaluate the importance of the kidneys in the clearance process of rFVIIa after iv administration to rats using a nephrectomy model.MATERIALS AND METHODS: A nephrectomized rat model was established and validated using inulin, a compound primarily cleared by the kidneys, as a test substance and several physiological parameters were monitored to ensure viability and robustness of the model. The model was then used for pharmacokinetic evaluation of renal clearance of rFVIIa. The pharmacokinetic parameters for rFVIIa were evaluated both by use of standard non-compartmental methods and by use of mixed effects methods, where a pharmacokinetic model was used to simultaneously model all data from healthy, sham operated, and nephrectomized rats.RESULTS: Nephrectomized animals showed stable rectal temperature, SpO2 and pulse and as expected, clearance of inulin was essentially abolished compared to control animals (p<0.001). For rFVIIa, nephrectomy resulted in a clearance and terminal half-life of 34mL/h/kg and 2.8h compared to 68mL/h/kg and1.9h in rats exposed to sham surgery (p<0.0001 for both parameters).CONCLUSION: The present data show that about 50{\%} of the total clearance of rFVIIa from circulation in rats under isoflurane anaesthesia is due to renal clearance.",
keywords = "The Faculty of Health and Medical Sciences, rFVIIa, Clearance, Kidney, Pharmacokinetics, Nephrectomy",
author = "Bill Vestergaard and Appa, {Rupa S.} and Jens Lykkesfeldt and Henrik Agers{\o}",
note = "Copyright {\circledC} 2014 Elsevier Ltd. All rights reserved.",
year = "2014",
doi = "10.1016/j.thromres.2014.03.034",
language = "English",
volume = "133",
pages = "1124--1129",
journal = "Thrombosis Research",
issn = "0049-3848",
publisher = "Pergamon Press",
number = "6",

}

RIS

TY - JOUR

T1 - The kidneys play an important role in the clearance of rFVIIa in rats

AU - Vestergaard, Bill

AU - Appa, Rupa S.

AU - Lykkesfeldt, Jens

AU - Agersø, Henrik

N1 - Copyright © 2014 Elsevier Ltd. All rights reserved.

PY - 2014

Y1 - 2014

N2 - INTRODUCTION: Previous distribution and histological studies have indicated that the kidneys and renal proximal tubular cells play a role in clearance of rFVIIa. However, the relative importance of the kidneys in clearance of rFVIIa has not previously been addressed. The objective of the present study was to evaluate the importance of the kidneys in the clearance process of rFVIIa after iv administration to rats using a nephrectomy model.MATERIALS AND METHODS: A nephrectomized rat model was established and validated using inulin, a compound primarily cleared by the kidneys, as a test substance and several physiological parameters were monitored to ensure viability and robustness of the model. The model was then used for pharmacokinetic evaluation of renal clearance of rFVIIa. The pharmacokinetic parameters for rFVIIa were evaluated both by use of standard non-compartmental methods and by use of mixed effects methods, where a pharmacokinetic model was used to simultaneously model all data from healthy, sham operated, and nephrectomized rats.RESULTS: Nephrectomized animals showed stable rectal temperature, SpO2 and pulse and as expected, clearance of inulin was essentially abolished compared to control animals (p<0.001). For rFVIIa, nephrectomy resulted in a clearance and terminal half-life of 34mL/h/kg and 2.8h compared to 68mL/h/kg and1.9h in rats exposed to sham surgery (p<0.0001 for both parameters).CONCLUSION: The present data show that about 50% of the total clearance of rFVIIa from circulation in rats under isoflurane anaesthesia is due to renal clearance.

AB - INTRODUCTION: Previous distribution and histological studies have indicated that the kidneys and renal proximal tubular cells play a role in clearance of rFVIIa. However, the relative importance of the kidneys in clearance of rFVIIa has not previously been addressed. The objective of the present study was to evaluate the importance of the kidneys in the clearance process of rFVIIa after iv administration to rats using a nephrectomy model.MATERIALS AND METHODS: A nephrectomized rat model was established and validated using inulin, a compound primarily cleared by the kidneys, as a test substance and several physiological parameters were monitored to ensure viability and robustness of the model. The model was then used for pharmacokinetic evaluation of renal clearance of rFVIIa. The pharmacokinetic parameters for rFVIIa were evaluated both by use of standard non-compartmental methods and by use of mixed effects methods, where a pharmacokinetic model was used to simultaneously model all data from healthy, sham operated, and nephrectomized rats.RESULTS: Nephrectomized animals showed stable rectal temperature, SpO2 and pulse and as expected, clearance of inulin was essentially abolished compared to control animals (p<0.001). For rFVIIa, nephrectomy resulted in a clearance and terminal half-life of 34mL/h/kg and 2.8h compared to 68mL/h/kg and1.9h in rats exposed to sham surgery (p<0.0001 for both parameters).CONCLUSION: The present data show that about 50% of the total clearance of rFVIIa from circulation in rats under isoflurane anaesthesia is due to renal clearance.

KW - The Faculty of Health and Medical Sciences

KW - rFVIIa

KW - Clearance

KW - Kidney

KW - Pharmacokinetics

KW - Nephrectomy

U2 - 10.1016/j.thromres.2014.03.034

DO - 10.1016/j.thromres.2014.03.034

M3 - Journal article

VL - 133

SP - 1124

EP - 1129

JO - Thrombosis Research

JF - Thrombosis Research

SN - 0049-3848

IS - 6

ER -

ID: 124440395