Fosaprepitant and Aprepitant for Chemotherapy-Induced Nausea and Vomiting in Children

Marcia L. Buck, PharmD, FCCP, FPPAG, BCPPS

Disclosures

Pediatr Pharm. 2018;24(6) 

In This Article

Pharmacokinetics

Fosaprepitant is converted to aprepitant via enzymatic conversion in the lungs, ileum, liver, and kidney.[1] Following administration of a single 150 mg fosaprepitant dose infused over 20 minutes, the mean maximum plasma concentration (Cmax) of aprepitant was 4.2 ± 1.2 mcg/mL, with a mean area under the concentration time curve (AUC) of 37.4 ± 14.8 mcg·hr/mL. Plasma concentrations of fosaprepitant were undetectable within 30 minutes of completion of the infusion. Aprepitant is more than 95% protein bound, with an average volume of distribution of 70 L. Aprepitant undergoes extensive hepatic metabolism, primarily via CYP3A4 and with minor metabolism by CYP1A2 and CYP2C19. Seven metabolites have been identified in human plasma, with little or no pharmacologic activity. The half-life of aprepitant ranges from 9 to 13 hours in adults.

The pharmacokinetic profile of fosaprepitant was investigated by the manufacturer using both study results of patients 6 months to 17 years of age and a simulated model of single and 3-day treatment regimens.[1] Following a 5 mg/kg IV dose in the younger age group, the aprepitant Cmax was 3.3 mcg/mL with an AUC of 32.7 mcg·hr/mL. In the 2 to 6 years group and the 6 to 12 years group given a dose of 4 mg/kg, the aprepitant Cmax values were 3.1 mcg/mL and 3.6 mcg/mL, respectively, with AUC values of 28.2 mcg·hr/mL and 35.2 mcg·hr/mL. Patients 12–17 years of age who received a 150 mg dose had similar values, with an aprepitant Cmax of 3.4 mcg/mL and AUC of 29.4 mcg·hr/mL. After a 3-day regimen of an IV dose and two oral 2 mg/kg or 80 mg doses, AUC values for the same groups were 16.6 mcg·hr/mL, 20.2 mcg·hr/mL, 25.7 mcg·hr/mL, and 18 mcg·hr/mL. All values were similar to those reported in adults.

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