Pharmacokinetics of low molecular weight heparins in thrombosis, complicate the treatment of children with cancer

Abstract

Objective: to evaluate the pharmacokinetics of nadroparin and dalteparin in thrombosis complicating the treatment of children with malignant neoplasms.Materials and methods. The results of 52 pharmacokinetic studies performed in 34 patients with malignant neoplasms, whose treatment was complicated by venous thrombosis, were analyzed. The age of the patients is from 7 to 18 years, he median is 14.5 years. Depending on the value of daily dose and type of heparin administered, the results of pharmacokinetic studies were divided into 6 groups. Dalteparin sodium: during period of chemotherapy induced thrombocytopenia, subcutaneous injection at a dose of 51.0 (40.0-72.0) anti Xa IU/kg every 12 hours - 6 studies; subcutaneous injection every 12 hours at a dose of 100.5 (91.0-141.0) anti Xa IU/kg - 18 observations; long-term continuous administration at a constant rate at a daily dose of 201.0 (180.0-265.0) anti Xa IU/kg - 6 pharmacokinetic observations. Nadroparin calcium: 62.0 (53.0-71.0) anti Xa IU/kg every 12 hours - 6 studies; 93.5 (80.0-117.0) anti Xa IU/kg every 12 hours - 10 observations; subcutaneous injection at a dose of 203.0 (170.0-236.0) anti Xa IU/kg once a day - 6 pharmacokinetic observations.Results. At steady-state, the area under the pharmacokinetic curve (AUC) of dalteparin and nadroparin, regardless of the mode of administration, depended on the maximum specific activity and half-life. No relationship was found for dalteparin between AUC and endogenous creatinine clearance. In contrast to dalteparin, the AUC after administration of na-droparin was closely related to endogenous creatinine clearance. The increase in chronometric indices indirectly reflected the presence of an anticoagulant in the blood, but did not allow an objective assessment of therapeutic effect achievement, recorded by the degree of thrombin generation inhibition.Conclusion. There were no significant advantages of nadroparin compared with dalteparin when using in comparable doses in the case of venous thrombosis, complicated the treatment of children with malignant neoplasms. Subcutaneous administration of 50 % nadroparin calcium daily dose with 12 hours interval is preferred over a single administration of 100 % daily dose every 24 hours. It is mandatory to monitor the administration of low molecular weight heparins in children with oncological diseases in order to make a decision on the adequacy of anticoagulant dose to the therapeutic range.