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



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.



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.



The pharmacokinetic properties obtained here for intravenous peramivir are consistent with the previously reported clinical efficacy and safety of this antiviral.
Medical Affairs Department, Shionogi & Co., Ltd, Osaka, Japan.
Yutaka
Y
Saisho
Clinical Research Department, Shionogi & Co., Ltd, Osaka, Japan.
Toru
T
Ishibashi
Clinical Research Department, Shionogi & Co., Ltd, Osaka, Japan.
Hidenori
H
Fukuyama
CPC Clinical Trial Hospital, Kagoshima, Japan.
Hiroyuki
H
Fukase
Shionogi & Co., Ltd, Tokyo, Japan.
Jingoro
J
Shimada
D000146:Acids, Carbocyclic; D061605:Administration, Intravenous; D000328:Adult; D000998:Antiviral Agents / Q000097:blood / Q000493:pharmacokinetics*; D019540:Area Under Curve; D003517:Cyclopentanes / Q000097:blood / Q000493:pharmacokinetics*; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004791:Enzyme Inhibitors / Q000097:blood / Q000493:pharmacokinetics*; D005260:Female; D015870:Gene Expression; D006146:Guanidines / Q000097:blood / Q000493:pharmacokinetics*; D064368:Healthy Volunteers; D006801:Humans; D009980:Influenza A virus / Q000187:drug effects / Q000201:enzymology; D007251:Influenza, Human / Q000188:drug therapy; D008297:Male; D009439:Neuraminidase / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D061214:Patient Safety; D014764:Viral Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism
D000146:Acids, Carbocyclic; D000998:Antiviral Agents; D003517:Cyclopentanes; D004791:Enzyme Inhibitors; D006146:Guanidines; D014764:Viral Proteins; D009439:Neuraminidase; C414210:peramivir