Titre du document / Document title

Tinzaparin and enoxaparin given at prophylactic dose for eight days in medical elderly patients with impaired renal function : A comparative pharmacokinetic study

Auteur(s) / Author(s)

MAHE Isabelle ⁽¹⁾ ; AGHASSARIAN Manvel ⁽¹⁾ ; DROUET Ludovic ⁽²⁾ ; BAL DIT-SOLLIER Claire ⁽²⁾ ; LACUT Karine ⁽³⁾ ; HEILMANN Jean-Jacques ⁽⁴⁾ ; MOTTIER Dominique ⁽³⁾ ; BERGMANN Jean-Francois ⁽¹⁾ ;

Affiliation(s) du ou des auteurs / Author(s) Affiliation(s)

⁽¹⁾ Internal Medicine DepartmentA, Lariboisière Hospital, Paris, FRANCE
⁽²⁾ Hematology Laboratory, Lariboisière Hospital, Paris, FRANCE
⁽³⁾ Equipe Accueil, La Cavale Blanche Hospital Brest, FRANCE
⁽⁴⁾ LEO-Pharma, Saint Quentin enYvelines, FRANCE

Résumé / Abstract

Low-molecular-weight heparins (LMWHs) accumulate in patients with impaired renal function. As this accumulation depends on heparin chain length and subsequent reticulo-endothelial/renal elimination, LMWHs might have different pharmacodynamic profiles.The primary objective was to examine if any accumulation effect of two LMWHs, enoxaparin and tinzaparin, occurred after repeated administration of a prophylactic dose over eight days in elderly patients (age >75 years) with creatinine clearance between 20 and 50 ml/min and body weight <65Kg. Patients were openly randomized to two groups (enoxaparin 4,000 IU or tinzaparin 4,500 IU once daily).Anti-Xa was measured on day I and day 8. Blood samples were taken at 0,2, 4,5,6,9,12,16 and 24 hours.The primary end point was the accumulation factor calculated as a ratio between the maximal anti-Xa activity on day I and day 8. Fifty-five patients were included (mean age 87.9 ±5.5 ).The creatinine clearance was 34.7 ± 11.4 ml/min; the body weight was 52.3 ± 8.6 kg.The accumulation factor defined was not significant for tinzaparin (1.05, p=0.29) while it was significantly enhanced for enoxaparin (1.22, p <0.0001). In this pharmacodynamic study performed in elderly patients with impaired renal function,a statistically significant accumulation effect was observed after eight days of prophylactic treatment with enoxaparin but not with tinzaparin, which are two LMWHs with different chain lengths.Trials based on clinical end points should be conducted to evaluate the clinical relevance of these observations.

Revue / Journal Title

Thrombosis and haemostasis   ISSN 0340-6245   CODEN THHADQ 

Source / Source

2007, vol. 97, n^o4, pp. 581-586 [6 page(s) (article)] (35 ref.)

Langue / Language

Anglais

Editeur / Publisher

Schattauer, Stuttgart, ALLEMAGNE  (1976) (Revue)

Mots-clés anglais / English Keywords

Kidney disease ; Urinary system disease ; Vascular disease ; Cardiovascular disease ; Human ; Pharmacokinetics ; Comparative study ; Renal function ; Renal failure ; Elderly ; Thrombosis ; Medicine ; Dose ; Enoxaparin sodium ; Prevention ; Low molecular weight heparin ; Tinzaparin sodium ;

Mots-clés français / French Keywords

Rein pathologie ; Appareil urinaire pathologie ; Vaisseau sanguin pathologie ; Appareil circulatoire pathologie ; Homme ; Pharmacocinétique ; Etude comparative ; Fonction rénale ; Insuffisance rénale ; Personne âgée ; Thrombose ; Médecine ; Dose ; Enoxaparine sodique ; Prévention ; Héparine bas poids moléculaire ; Tinzaparine sodique ;

Mots-clés espagnols / Spanish Keywords

Riñón patología ; Aparato urinario patología ; Vaso sanguíneo patología ; Aparato circulatorio patología ; Hombre ; Farmacocinética ; Estudio comparativo ; Función renal ; Insuficiencia renal ; Anciano ; Trombosis ; Medicina ; Dosis ; Enoxaparina sódica ; Prevención ; Heparina bajo peso molecular ; Tinzaparina sódica ;

Mots-clés d'auteur / Author Keywords

LMWHs ; thromboprophylaxis ; elderly ; renal insufficiency ;

Localisation / Location

INIST-CNRS, Cote INIST : 10255, 35400014341276.0130