Population Pharmacokinetics of Human Antithrombin Concentrate in Pediatric Patients

Abstract

Aims

Antithrombin is increasingly used in pediatric patients, yet there are few age-specific pharmacokinetic data to guide dosing. We aim to describe the pharmacokinetic profile of human (plasma-derived) antithrombin concentrate in pediatric patients.

Methods

A retrospective review of 5 years of patients < 19 years of age admitted to our institution who received antithrombin concentrate, were not on mechanical circulatory support and had baseline (pre-dose) and post-dose plasma antithrombin activity levels available for analysis, was performed. Demographic and laboratory variables, antithrombin dosing information and use of continuous infusion unfractionated heparin were collected. Population pharmacokinetic analysis was performed with bootstrap analysis. The model developed was tested against a validation dataset from a cohort of similar patients and predictive value was calculated.

Results

A total 184 patients met study criteria (male 46.7%, median age (years) 0.35 (IQR 0.07-3.9). A median of 2 antithrombin doses (IQR1-4) were given to patients (Dose of 46.3+13.6 units/kg) with median of 3 (IQR 2-7) post-dose levels per patient. Continuous infusion unfractionated heparin was administered in 87.5% of patients at a mean dose of 34.1+22.7 units/kg/hour. A one compartment exponential error model best fit the data, and significant covariates included allometrically scaled weight on clearance and volume of distribution, unfractionated heparin dose on clearance, and baseline antithrombin activity level on volume of distribution. The model resulted in a median -1.75% prediction error (IQR -11.75% - 6.5%) when applied to the validation dataset (n=30).

Conclusions

Antithrombin pharmacokinetics are significantly influenced by concurrent use of unfractionated heparin and baseline anthrombin activity.

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