Pharmacokinetics and safety of intravenous peramivir, neuraminidase inhibitor of influenza virus, in healthy Japanese subjects.

Abstract

BACKGROUND:

Intravenous peramivir is a potent neuraminidase (NA) inhibitor with activity against influenza A and B viruses. The early use of NA inhibitors has been shown to reduce mortality in influenza patients.

METHODS:

To evaluate the pharmacokinetics of peramivir and confirm the safety and tolerability of multiple infusions of peramivir in healthy Japanese subjects, two Phase I, single-centre, randomized, double-blind and placebo-controlled studies consisting of a multiple-dose study and a high-dose study were conducted.

RESULTS:

Multiple intravenous infusions of peramivir were well tolerated up to 800 mg once a day and 400 mg twice daily for 6 days. Dose proportionalities for maximum plasma concentration (Cmax) and area under the plasma concentration-time curve (AUC) were established up to the 800 mg dose. Approximately 90% of unchanged peramivir was excreted into urine within 12 h after treatment with 800 mg of peramivir. The peramivir plasma and upper respiratory tract fluid levels were significantly higher than the 50% inhibition concentrations for NA enzyme activity (IC50) of epidemic influenza viruses, including those harbouring the H274Y mutation.

CONCLUSIONS:

The pharmacokinetic properties obtained here for intravenous peramivir are consistent with the previously reported clinical efficacy and safety of this antiviral.

• Authors: Yutaka Saisho, Toru Ishibashi, Hidenori Fukuyama, Hiroyuki Fukase, Jingoro Shimada
• Journal: Antiviral therapy (Antivir Ther) Vol. 22 Issue 4 Pg. 313-323 ( 2017) ISSN: 2040-2058 [Electronic] England
• PMID: 27805571 (Publication Type: Clinical Trial, Phase I, Journal Article, Randomized Controlled Trial)

Chemical References

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

Topics

• Acids, Carbocyclic
• Administration, Intravenous
• Adult
• Antiviral Agents (blood, pharmacokinetics)
• Area Under Curve
• Cyclopentanes (blood, pharmacokinetics)
• Double-Blind Method
• Drug Administration Schedule
• Enzyme Inhibitors (blood, pharmacokinetics)
• Female
• Gene Expression
• Guanidines (blood, pharmacokinetics)
• Healthy Volunteers
• Humans
• Influenza A virus (drug effects, enzymology)
• Influenza, Human (drug therapy)
• Male
• Neuraminidase (antagonists & inhibitors, genetics, metabolism)
• Patient Safety
• Viral Proteins (antagonists & inhibitors, genetics, metabolism)