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Pharmacokinetics of dalteparin, nadroparin and bemipar in thrombosis in children, adolescents and young adults with cancer


Hematology & Transfusion International Journal
Dmitriev VV, Lipay NV, Begun IV

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Abstract

Objective: To compare the pharmacokinetics of Daltetaprine, Nadroparin and Bemiparin in pediatric and young adult patients with malignancies complicated by thrombosis.

Materials and methods: We examined 34 patients aged 7 to 24 years (median 17 years) with deep vein thrombosis, which complicated the protocol treatment of children and young adult patients with cancer.

Results: In a3.0 (1.0-3.0) hours after subcutaneous administration of dalteparin 100.5 (91.0-141.0) anti Xa IU/kg, nadroparin 93.5 (90.0-111.0 ) anti-Xa IU/kg and bemiparin 86.0 (79.0-100.0) anti-Xa IU/kg showed an increase (compared to baseline p<0.01; paired T-test) in specific activity of LMWH (Cmax) in blood up to 0.65 (0.53-0.76) anti Xa IU/ ml, 0.66 (0.41-0.72) anti Xa IU/ml and 0.57 (0.53-0.65 ) anti Xa IU/ml, respectively. The achievement of Cmaxwas accompanied by inhibition of thrombin generation expressed to varying degrees and a hypocoagulant effect. T½ of dalteparin 6.5 (3.6-9.6) hours, nadroparin 5.9 (3.6-8.2) hours and bemiparin 7.4 (4.7-10.5) hours did not depend (G=-0.14 and p=0.425; G=0.04 and p=0.83; G=0.09 and p=0.73, respectively) on the administered dose of LMWH. In contrast to dalteparin, there was a dependence of the T ½ value of nadroparin (G=0.35; p=0.03) and bemiparin (G=0.6; p=0.006) on endogenous creatinine clearance 111.0 (58.0-170, 0) ml•min-1 and 97.0 (28.0-205.0) ml•min-1. Therefore, longterm use of nadroparin calcium and bemiparin sodium, compared with dalteparin sodium, during the treatment of children with thrombosis requires more frequent monitoring of the efficacy and safety of antithrombotic therapy.

Conclusion: Control over the adequacy of the dose of LMWH can be performed at any stage of treatment. After reaching a steady state the specific activity of nadroparin, bemiparin and dalteparin should be recorded before the next subcutaneous injection and between 2 and 3 hours after administration. An increase in chronometric indicators indirectly reflects the presence of an anticoagulant in the blood, but does not allow an objective assessment of the achievement of a therapeutic effect. Routine determination of specific anti-Xa is not recommended.

Keywords

venous thromboss, malignant neoplasms, children, adolescents, young adults, anticoagulant therapy, low molecular weight heparin

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