Influenza viral load and peramivir kinetics after single administration and proposal of regimens for peramivir administration against resistant variants.

Abstract

We estimated the efficacy of the current single administration of peramivir on the basis of peramivir pharmacokinetics in the upper respiratory tract (URT) and determined the predictive peramivir concentration-time curve to assess its efficacy against viruses with decreased susceptibility to neuraminidase inhibitors. Serum, nasal swab, or aspiration samples were collected from 28 patients treated with 10 mg/kg body weight peramivir. The sequential influenza viral RNA load and susceptibility after peramivir administration were measured using a quantitative real-time reverse transcription-PCR and neuraminidase inhibition assay. The peramivir concentrations in the serum and URT after a single administration at 10 mg/kg were measured, and the predictive blood and URT peramivir concentration-time curves were determined to assess various administration regimens against resistant variants. The peramivir concentration decreased to <0.1% of the maximum concentration of drug in serum (Cmax) at 24 h after administration. Rapid elimination of peramivir from the URT by 48 h after administration may contribute to an increase in the influenza A viral load after day 3 but not to a decrease in the influenza B viral load, despite the absence of a decrease in the susceptibility to peramivir. A longer maintenance of a high level of peramivir in the URT is expected by divided administration rather than once-daily administration. When no clinical improvement is observed in patients with normal susceptibility influenza A and B, peramivir readministration should be considered. In severe cases caused by resistant variants, better inhibitory effectiveness and less frequent adverse events are expected by divided administration rather than once-daily administration with an increased dosage.

• Authors: Masatoki Sato, Masaki Ito, Shigeo Suzuki, Hiroko Sakuma, Aya Takeyama, Shinichi Oda, Masahiro Watanabe, Koichi Hashimoto, Kyohei Miyazaki, Yukihiko Kawasaki, Mitsuaki Hosoya
• Journal: Antimicrobial agents and chemotherapy (Antimicrob Agents Chemother) Vol. 59 Issue 3 Pg. 1643-9 (Mar 2015) ISSN: 1098-6596 [Electronic] United States
• PMID: 25547357 (Publication Type: Journal Article)
• Copyright: Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Chemical References

• Acids, Carbocyclic
• Antiviral Agents
• Cyclopentanes
• Enzyme Inhibitors
• Guanidines
• Viral Proteins
• Neuraminidase
• peramivir

Topics

• Acids, Carbocyclic
• Adolescent
• Antiviral Agents (administration & dosage, pharmacokinetics)
• Child
• Child, Preschool
• Cyclopentanes (administration & dosage, pharmacokinetics)
• Drug Resistance, Viral (drug effects)
• Enzyme Inhibitors (administration & dosage, pharmacokinetics)
• Female
• Guanidines (administration & dosage, pharmacokinetics)
• Humans
• Infant
• Influenza A virus (drug effects, metabolism)
• Influenza B virus (drug effects, metabolism)
• Influenza, Human (drug therapy)
• Kinetics
• Male
• Neuraminidase (antagonists & inhibitors)
• Viral Load (drug effects)
• Viral Proteins (metabolism)