ABSTRACT
OBJECTIVES: Determine the effect of exogenous antithrombin III administration on low molecular weight heparin anti-Xa levels in the context of enoxaparin dosing in infants. METHODS: A retrospective chart review of infants receiving concomitant antithrombin III and enoxaparin. The primary objective of this study was to determine the median change in anti-Xa level with antithrombin III supplementation. Secondary objectives were to analyze the median change in antithrombin III levels after administration of exogenous antithrombin III, the dosing of antithrombin III, and the dose of enoxaparin throughout therapy. For a safety analysis, any bleeding events were recorded. RESULTS: The study included 17 patients who received a total of 33 doses of antithrombin III. The median change in anti-Xa levels in infants receiving exogenous antithrombin III was 0.2 units/mL (p < 0.001). The median dose of antithrombin III was 50 units/kg and was administered when patients were receiving a median enoxaparin dose of 1.71 mg/kg. The median increase in antithrombin III levels was 16.5% (p < 0.001). CONCLUSIONS: These results demonstrated that administration of exogenous antithrombin III to infants who were being treated with enoxaparin results in a significant increase in anti-Xa levels. At this time, there is insufficient evidence to recommend routine administration of antithrombin III to infants on enoxaparin. However, antithrombin III supplementation could be considered a potential option for patients who are unable to adequately achieve therapeutic anti-Xa levels with enoxaparin alone.
ABSTRACT
OBJECTIVE: Phenobarbital is frequently used in pediatric patients for treatment and prophylaxis of seizures. Pharmacokinetic data for this patient population is lacking and would assist in dosing decisions. METHODS: A retrospective population pharmacokinetic analysis was designed for all pediatric patients <19 years of age initiated on phenobarbital at our institution from January 2011 to June 2017. Patients were included if they were initiated on intravenous or enteral phenobarbital for treatment or prophylaxis of seizures and had a serum phenobarbital concentration monitored while an inpatient. Data collection included the following: age, weight, height, gestational age, core body temperature, serum creatinine, blood urea nitrogen, aspartase aminotransferase, alanine aminotransferase, urine output over the prior 12 hours, phenobarbital doses and serum concentrations, and potential drug-drug interactions. Descriptive statistical methods were used to summarize the data. Pharmacokinetic analysis was performed with NONMEM and simulation was performed for doses of 10, 20, 30, and 40 mg kg-1 dose-1 , iv, followed by enteral doses of 3, 4, 5, and 6 mg kg-1 d-1 . RESULTS: A total of 355 patients (50.3% male, median gestational age 39 weeks (interquartile range [IQR] 35, 40), median age 0.28 years (IQR 0.06, 0.82). Median phenobarbital dose was enteral = 2.6 (IQR 1.9, 3.9) mg kg-1 dose-1 ; intravenous = 2.6 (IQR 2.2, 4.9) mg kg-1 dose-1 ) and mean serum concentration was 41.1 ± 23.9 mg/L at median 6.5 (IQR 2.9, 11.1) hours after a dose. A one-compartment proportional error model best fit the data where clearance and volume of distribution were allometrically scaled using fat-free mass. Significant covariates included serum creatinine, postmenstrual age, and drug-drug interactions on clearance, and age in years on volume of distribution. SIGNIFICANCE: Phenobarbital dosing of 30 mg kg-1 dose-1 ,iv, followed by 4 mg kg-1 d-1 had the highest probability of attaining a therapeutic concentration at 7 days. Postmenstrual age and drug-drug interactions should be incorporated into dosing decisions.
