Population Pharmacokinetics of Baloxavir Marboxil in Japanese Pediatric Influenza Patients

J Pharm Sci. 2019 Sep;108(9):3112-3117. doi: 10.1016/j.xphs.2019.04.010. Epub 2019 Apr 16.

Abstract

Baloxavir marboxil is a prodrug of baloxavir acid, an inhibitor of cap-dependent endonuclease, and suppresses the replication of influenza virus. The aim of this study was to investigate its pharmacokinetic characteristics in Japanese pediatrics. Population pharmacokinetic analysis was conducted for baloxavir acid with 328 plasma concentration data points in a clinical study of 107 Japanese pediatric influenza patients. The plasma baloxavir acid concentration profiles were well captured by a 2-compartment model including first-order absorption and lag time. Body weight was considered to be the most crucial covariate, which affects clearance and volume of distribution. The body weight-based dose regimen (10 mg for 10 kg to less than 20 kg pediatrics, 20 mg for 20 kg to less than 40 kg pediatrics, and 40 mg for at least 40 kg pediatrics) for Japanese pediatrics can provide comparable exposure to baloxavir acid to that for adults. In conclusion, the population pharmacokinetic model would be useful to comprehend the characteristics of baloxavir acid pharmacokinetics in pediatric patients.

Keywords: Japanese; S-033188; baloxavir marboxil; cap-dependent endonuclease inhibitor; influenza; pediatrics; population pharmacokinetics.

MeSH terms

  • Adult
  • Age Factors
  • Antiviral Agents / administration & dosage
  • Antiviral Agents / pharmacokinetics*
  • Bayes Theorem
  • Biological Variation, Population / physiology*
  • Body Weight
  • Child
  • Child, Preschool
  • Dibenzothiepins
  • Dose-Response Relationship, Drug
  • Half-Life
  • Humans
  • Infant
  • Influenza, Human / blood
  • Influenza, Human / drug therapy*
  • Japan
  • Metabolic Clearance Rate / physiology
  • Models, Biological*
  • Morpholines
  • Oxazines / administration & dosage
  • Oxazines / pharmacokinetics*
  • Prodrugs / administration & dosage
  • Prodrugs / pharmacokinetics
  • Pyridines / administration & dosage
  • Pyridines / pharmacokinetics*
  • Pyridones
  • Thiepins / administration & dosage
  • Thiepins / pharmacokinetics*
  • Triazines / administration & dosage
  • Triazines / pharmacokinetics*

Substances

  • Antiviral Agents
  • Dibenzothiepins
  • Morpholines
  • Oxazines
  • Prodrugs
  • Pyridines
  • Pyridones
  • Thiepins
  • Triazines
  • baloxavir