Summary

In children, there is an increasing off-label use of low molecularweight heparin (LMWH). However, there is an absence of informationon dosing and pharmacokinetics of LMWH over allage groups.The objectives of the current study were to determinei) the once daily dose required to achieve anti-Xa levels of0.5–1.0 IU/mL, ii) the pharmacokinetics and iii) preliminarysafety data using tinzaparin.The study took the form of a singlecentre open-label Phase II study performed in 35 children requiringanticoagulation for treatment of thromboembolism. Agegroups studied were: 0-<2 months; 2 months-<1 year; 1-<5years; 5-<10 years; 10–16 years. Both population pharmacokineticanalysis using nonlinear mixed-effect modeling techniquesand model-independent pharmacokinetic methods were employed. Results showed a relationship of age and dose requirements,clearance, time to peak anti-Xa level and volume of distribution.Younger children required an increased dose, clearedtinzaparin more rapidly, had anti-Xa levels peak earlier and hadan increased volume of distribution. Younger children weremore likely to be below target range than older children,with upto 75% of children <1 year being below the target anti-Xa level.Four recurrences and one major bleed occurred. In conclusion,there is an inverse relationship of age on dose requirements relatedto volume of distribution, clearance and time to peak anti-Xa. Children <5 years likely require dose adjustment samples tobe drawn 2–3 hours post injection. Infants require anti-Xa levelsto be monitored at least twice m