HOMEPRODUCTSCOMPANYCONTACTFAQResearchDictionaryPharmaSign Up FREE or Login

Population pharmacokinetics of laninamivir and its prodrug laninamivir octanoate in healthy subjects and in adult and pediatric patients with influenza virus infection.

Abstract
Laninamivir octanoate (LO) is a new neuraminidase inhibitor for inhalation. The objectives of this study were to model the population pharmacokinetics of LO and its active metabolite laninamivir after inhaled administration of LO using a pooled population of healthy subjects, and adult and pediatric patients with influenza virus infection from 8 clinical studies, and to evaluate covariate effects on pharmacokinetics. The pharmacokinetics of LO and laninamivir in plasma and urine are well-described by structural models that consist of a 2-compartment model for LO with instantaneous bolus input and first-order elimination; and a 1-compartment model for laninamivir with formation of laninamivir via the metabolic pathway from LO in systemic circulation, entry of laninamivir from the respiratory tract compartment, and linear elimination. Creatinine clearance was identified as a covariate of apparent total clearance for LO and renal clearances for LO and laninamivir, with the largest effect on laninamivir exposure. Body weight was identified to affect distribution volumes of LO and laninamivir and the metabolic clearance of LO; however there was no notable effect on exposures across the wide body weight range evaluated. The population pharmacokinetic model also provides insight into the likely kinetics of drug disposition in the respiratory tract following inhaled administration.
AuthorsKazutaka Yoshihara, Hitoshi Ishizuka, Yuichi Kubo
JournalDrug metabolism and pharmacokinetics (Drug Metab Pharmacokinet) Vol. 28 Issue 5 Pg. 416-26 ( 2013) ISSN: 1880-0920 [Electronic] England
PMID23574886 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Antiviral Agents
  • Enzyme Inhibitors
  • Guanidines
  • Prodrugs
  • Pyrans
  • Sialic Acids
  • laninamivir
  • Neuraminidase
  • Zanamivir
Topics
  • Administration, Inhalation
  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Antiviral Agents (pharmacokinetics)
  • Child
  • Child, Preschool
  • Enzyme Inhibitors (pharmacokinetics)
  • Female
  • Guanidines
  • Humans
  • Influenza, Human (drug therapy)
  • Male
  • Middle Aged
  • Neuraminidase (antagonists & inhibitors)
  • Prodrugs (metabolism, pharmacokinetics)
  • Pyrans
  • Sialic Acids
  • Zanamivir (administration & dosage, analogs & derivatives, metabolism, pharmacokinetics, urine)

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!


Choose Username:
Email:
Password:
Verify Password:
Enter Code Shown: