Evaluation of the pharmacokinetics of dalteparin in patients with renal insufficiency
| Autor: | H Achenbach, C Preiss, A Siegemund, Rainer Preiss, J Stöbe |
|---|---|
| Rok vydání: | 2006 |
| Předmět: |
Adult
Dalteparin Male medicine.medical_specialty Adolescent Metabolic Clearance Rate Lipoproteins medicine.medical_treatment Urology Renal function Severity of Illness Index Tissue factor pathway inhibitor Pharmacokinetics Reference Values Renal Dialysis Severity of illness Humans Medicine Pharmacology (medical) In patient Renal Insufficiency Pharmacology business.industry Anticoagulants Heparin Venous blood Middle Aged Surgery Creatinine Factor Xa Female Prothrombin Hemodialysis business Factor Xa Inhibitors medicine.drug |
| Zdroj: | Int. Journal of Clinical Pharmacology and Therapeutics. 44:455-465 |
| ISSN: | 0946-1965 |
| Popis: | The pharmacokinetics of the low-molecular weight heparin (LMWH), dalteparin, was evaluated after a single intravenous bolus injection of 50 IU anti-Xa/kg in 8 healthy volunteers, 8 patients with moderate/severe renal failure (Cl(crea) 13.1-56.5 ml/min) and 8 hemodialysis patients. Venous blood samples were taken over a 1-day period to determine anti-Xa activity, anti-IIa activity and plasma levels of free tissue factor pathway inhibitor (free TFPI). Plasma anti-Xa and anti-IIa activities were measured using chromogenic assays and free TFPI levels using an ELISA technique. The anti-Xa clearance was significantly decreased (p < 0.05) in both groups with renal insufficiency when compared with healthy volunteers. There was a positive correlation between creatinine clearance and anti-Xa clearance in the healthy volunteers and patients with moderate/severe renal failure. The anti-Ila activity was characterized by 3- to 4-fold lower plasma concentrations and faster elimination compared with the anti-Xa activity. In patients with moderate/severe renal failure the elimination of anti-lla was only slightly decreased, whereas in hemodialysis patients anti-Ila clearance was significantly decreased (p < 0.01). There was no correlation between creatinine clearance and anti-IIa clearance. The baseline mean free TFPI plasma levels in the two groups with renal insufficiency were significantly higher (p < 0.01) than in healthy volunteers. Dalteparin administration induced a transient, 6.0- to 8.1-fold increase in the free TFPI values in the three study groups. Dalteparin induced an increase in C(max) and AUC(0 - infinity) values of free TFPI in the two groups with renal insufficiency that was higher than in healthy volunteers. No bleeding complications occurred during the study. In conclusion, this is the first report showing retarded elimination of dalteparin and enhanced free TFPI plasma levels induced by a LMWH in patients with renal insufficiency. |
| Databáze: | OpenAIRE |
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