RENAL ELIMINATION OF TINZAPARIN VERSUS ENOXAPARIN IN NORMAL VERSUS NEPHRECTOMIZED RATS

Abstract number: P-W-629

Johansen¹ K.B., Schroeder¹ M., Lundtorp¹ L., Mousa² S.A.

¹¹Research, Leo Pharma, Ballerup, Denmark ²²Pharmaceutical Research Institute, Albany College of Pharmacy, Albany, NY, United States

How-to-cite Johansen KB, Schroeder M, Lundtorp L, Mousa SA. RENAL ELIMINATION OF TINZAPARIN VERSUS ENOXAPARIN IN NORMAL VERSUS NEPHRECTOMIZED RATS. J Thromb Haemost 2007; 5 Supplement 2: P-W-629

Abstract

Introduction: Heparin and LMWH are cleared renally, so patients who have kidney failure are at higher risk of bleeding; dose adjustment has to be made based on kidney function. The purpose of this study is to determine whether two different LMWHs (tinzaparin and enoxaparin) would accumulate in animals with severe kidney failure as compared to normal rats.

Methods: Tinzaparin and enoxaparin were administered to nephrectomized or non-nephrectomized rats at equivalent anti-Xa units/kg. Urine samples were collected over 24 hours post-dosing, and urinary anti-Xa activity was measured.

Results: The urinary elimination of the tinzaparin and enoxaparin was significantly different in normal rats, with greater renal eliminations of enoxaparin (P <0.001) as compared to tinzaparin at either 87.5 or 175 IU/kg, IV. Tinzaparin renal elimination did not significantly differ in normal versus nephrectomized rats. In contrast, enoxaparin elimination was significantly reduced (P <0.001) in nephrectomized as compared to normal rats.

Table:

	Normal Rats	Nephrectomized Rats
Tinzaparin	22.4 13.3	19.2 3.3
Enoxaparin	64.2 11.6	26.7 9.5**
** P < 0.001 nephrectomized versus normal animals; data represent mean SD.

Conclusions: These data indicated different renal elimination kinetics of tinzaparin versus enoxaparin and suggested that tinzaparin might be administered in renal failure subjects without the need for dose adjustment or monitoring as compared to other LMWHs. This warrants further detailed clinical pharmacokinetic studies in subjects with renal failure. These elimination characteristics of tinzaparin are the basis of the ongoing Innohep in Renal Insufficiency Study (IRIS).

To cite this abstract use the following format:

Journal of Thrombosis and Haemostasis 2007; Volume 5, Supplement 2: abstract number

Session Details

Date:	01/08/2007
Time:	00:00-00:00
Session name:	XXIst ISTH Congress
Subject:
Location:	Oxford, UK
Presentation type:
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