Pharmacokinetics of dalteparin and nadroparin for thromboses in children with oncological diseases

Abstract

Objective: evaluate the pharmacokinetics and pharmacodynamics of nadroparin and dalteparin in thrombosis that occurred in children with malignant neoplasms. Materials and methods: The results of 52 pharmacokinetic studies involving 34 patients with oncological diseases, whose treatment was complicated by venous thrombosis, were analyzed. The median age of patients was 14.5 (7–18) years. Depending on the daily dose and the type of heparin administered, the results of pharmacokinetic studies were divided into 6 groups. Dalteparin sodium: against the background of chemo-induced thrombocytopenia, subcutaneous administration of dalteparin at a dose of 51.0 (40.0–72.0) anti-Xa IU/kg every 12 hours – 6 observations; subcutaneous injection every 12 hours at a dose of 100.5 (91.0–141.0) anti-Xa IU/kg – 18 observations; long-term continuous intravenous infusion at a constant rate at a daily dose of 201.0 (180.0–265.0) anti-Xa IU/kg - 6 observations. Nadroparin calcium: 62.0 (53.0-71.0) anti-Xa IU/kg every 12 hours - 6 observations; 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 observations. Results: We confirmed that in the acute period of thrombosis in children, the most optimal way to administer low molecular weight heparin is intravenous infusion of dalteparin sodium at a constant rate. Subcutaneous injection of 50% of the daily dose of LMWH at intervals of 12 hours is preferable to a single injection of 100% of the daily dose every 24 hours. There were no significant advantages of nadroparin compared with dalteparin when using anticoagulants in comparable doses in case of venous thrombosis, which complicated the treatment of children with malignant neoplasms. Conclusion: Control over the adequacy of the dose of LMWH can be performed at any stage of treatment. The specific anti-Xa activity of nadroparin and dalteparin needs to be checked before the next subcutaneous injection and between 3 and 4 hours after administration. An increase in chronometric indicators of blood coagulation indirectly reflects the presence of an anticoagulant in the blood, but does not allow an objective assessment of the achievement of a therapeutic effect.