Pharmacokinetic Studies of Standard Heparin and Low Molecular Weight Heparin in Patients with Chronic Renal Failure

Folléa, Gilles; Laville, Maurice; Pozet, N; Dechavanne, M

doi:10.1159/000215284

Cited by 23 publications

(14 citation statements)

References 8 publications

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“…The increased Ang A/Ang II ratio in patients with stage 5 chronic kidney disease may either indicate an increased activity of decarboxylase in human mononuclear cells from patients with chronic kidney disease stage 5, a reduced enzymatic degradation of Ang A in these patients, or renal excretion. An increase of the Ang A half-life is not unlikely, because modifications of half life of low molecular proteins or peptides in chronic renal failure patients are described frequently (eg, 13,14 ). Presently it is unknown whether the increased Ang A/Ang II ratio in plasma may be related to well-known uremic complications in patients with chronic kidney disease stage 5.…”

Section: Discussionmentioning

confidence: 99%

Mass-Spectrometric Identification of a Novel Angiotensin Peptide in Human Plasma

Jankowski

Vanholder

Giet

et al. 2007

ATVB

165

176

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Objective-Angiotensin peptides play a central role in cardiovascular physiology and pathology. Among these peptides, angiotensin II (Ang II) has been investigated most intensively. However, further angiotensin peptides such as Ang 1-7, Ang III, and Ang IV also contribute to vascular regulation, and may elicit additional, different, or even opposite effects to Ang II. Here, we describe a novel Ang II-related, strong vasoconstrictive substance in plasma from healthy humans and end-stage renal failure patients. ]-Ang II, in the following named Angiotensin A (Ang A), is most likely generated enzymatically. In the presence of mononuclear leukocytes, Ang II is converted to Ang A by decarboxylation of Asp 1 . Ang A has the same affinity to the AT 1 receptor as Ang II, but a higher affinity to the AT 2 receptor. In the isolated perfused rat kidney, Ang A revealed a smaller vasoconstrictive effect than Ang II, which was not modified in the presence of the AT2 receptor antagonist PD 123319, suggesting a lower intrinsic activity at the AT 1 receptor. Ang II and Ang A concentrations in plasma of healthy subjects and end-stage renal failure patients were determined by matrix-assisted laser desorption/ionisation mass-analysis, because conventional enzyme immunoassay for Ang II quantification did not distinguish between Ang II and Ang A. In healthy subjects, Ang A concentrations were less than 20% of the Ang II concentrations, but the ratio Ang A / Ang II was higher in end-stage renal failure patients. Conclusion-Ang

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Section: Discussionmentioning

confidence: 99%

Mass-Spectrometric Identification of a Novel Angiotensin Peptide in Human Plasma

Jankowski

Vanholder

Giet

et al. 2007

ATVB

165

176

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“…In 1986, Follea ct al. [63] compared the kinet ic patterns of enoxaparin and UFH, both giv en i.v. in patients with chronic renal failure.…”

Section: Renal Insufficiencymentioning

confidence: 99%

Low-Molecular-Weight Heparins: An Overview of their Pharmacodynamics, Pharmacokinetics and Metabolism in Humans

Frydman¹

1996

Pathophysiol Haemos Thromb

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Low-molecular-weight heparins (LMWHs) comprise a group in the class of antithrombotic medications, a class headed by unfractionated heparin (UFH). The LMWHs, with mean molecular weights of 4.0-6.0 kD, differ in their individual manufacturing processes, the distribution of their fragment molecular weights, their in vitro potency (anti-Xa, antithrombin and anticoagulant activities) and, consequently, in their biodynamic patterns, recommended dose regimen, and efficacy/safety ratio. Their drug disposition profiles have been evaluated using two significant markers of their pharmacodynamic activity, namely anti-Xa and anti-IIa activities. Since they are mainly administered subcutaneously, then compared to UFH, they are almost completely absorbed (F > 90%) and, in contrast to UFH, those for which data are available in the literature exhibit linear pharmacokinetics with proportionality between anti-Xa (and anti-IIa in some cases) plasma concentration and dose, and stationary distribution volume and clearance processes when the dosage is increased. Their distribution volume is close to the blood volume, they are partially metabolized by desulphatation and depolymerization, but urinary excretion of anti-Xa activity for enoxaparin, dalteparin and nadroparin, all given at doses for prevention of venous thrombosis, is between 5 and 10% of the injected dose. However, these LMWHs differ in the extent of their non-renal clearance, resulting in different apparent elimination half-life values and relative apparent bioavailability. When considering certain at-risk situations, using doses for preventing thromboembolism, the LMWHs do not significantly cross the placenta of pregnant women and their excretion profiles are only slightly altered in severe (endogenous creatinine clearance less than 15 ml/min) renal disease patients when given at doses recommended for prevention of venous thromboembolism. Because of the differences among LMWHs, the clinical profile of a given LMWH cannot be extrapolated to another one or generalized to the whole LMWH family.

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“…64,65 Unfractionated Heparin Unfractionated heparin (UFH) clearance occurs by a rapid saturable mechanism of the endothelium and reticuloendothelial system and a slower nonsaturable mechanism through the kidneys. 64,66 Half-life is slightly prolonged (1.5-fold) in renal impairment, especially at higher doses, when renal elimination is more significant. However, UFH is initially used at normal dose in renal impairment with titration based on activated partial thromboplastin time monitoring and response.…”

Section: Anticoagulants Antiplatelet Agents Thrombolytics and Hemomentioning

confidence: 99%

Principles of Drug Therapy, Dosing, and Prescribing in Chronic Kidney Disease and Renal Replacement Therapy

Cervelli¹,

Russ²

2010

Comprehensive Clinical Nephrology

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Pharmacokinetic Studies of Standard Heparin and Low Molecular Weight Heparin in Patients with Chronic Renal Failure

Cited by 23 publications

References 8 publications

Mass-Spectrometric Identification of a Novel Angiotensin Peptide in Human Plasma

Mass-Spectrometric Identification of a Novel Angiotensin Peptide in Human Plasma

Low-Molecular-Weight Heparins: An Overview of their Pharmacodynamics, Pharmacokinetics and Metabolism in Humans

Principles of Drug Therapy, Dosing, and Prescribing in Chronic Kidney Disease and Renal Replacement Therapy

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