Antimicrob Agents Chemoter. CS-8958 (laninamivir prodrug), a long-acting neuraminidase inhibitor, shows superior anti-influenza virus activity after a

[Giuseppe]

CS-8958 (laninamivir prodrug), a long-acting neuraminidase inhibitor, shows superior anti-influenza virus activity after a single administration. (Antimicrob Agents Chemoter., abstract, edited, RA-1010)

Antimicrob Agents Chemother. 2010 Jan 4. [Epub ahead of print]

CS-8958 (laninamivir prodrug), a long-acting neuraminidase inhibitor, shows superior anti-influenza virus activity after a single administration.

Kubo S, Tomozawa T, Kakuta M, Tokumitsu A, Yamashita M. - Biological Research Laboratories IV, Daiichi Sankyo Co. Ltd., 1-2-58, Hiromachi, Shinagawa, Tokyo 140-8710, Japan.

For the treatment and prophylaxis of influenza, two neuraminidase (NA) inhibitors, zanamivir (Relenza(TM)) and oseltamivir phosphate (Tamiflu(TM)), have been licensed. We have reported on laninamivir (code name, R-125489), a novel neuraminidase inhibitor, and have discovered that CS-8958, laninamivir prodrug, worked as a long acting neuraminidase inhibitor in a mouse influenza virus infection model when it was intranasally administered. In this paper, CS-8958 administered just once 7 days before infection showed significant efficacy in vivo. Then, the efficacy by a single administration of CS-8958 after viral infection was compared with that by repeated administrations of oseltamivir phosphate or zanamivir in mice and ferrets and CS-8958 showed superior or similar efficacy to the two licensed NA inhibitors. CS-8958 also significantly reduced the virus titers of an oseltamivir-resistant H1N1 virus with a neuraminidase H274Y substitution in a mouse infection model. These results suggest that, since CS-8958 is characteristically long lasting in the lungs, it may be ideal for the prophylaxis and treatment of influenza.

PMID: 20047917 [PubMed - as supplied by publisher]
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[gsgs]

Re: Antimicrob Agents Chemoter. CS-8958 (laninamivir prodrug), a long-acting neuraminidase inhibitor, shows superior anti-influenza virus activity after a single administration.

when you go to the Daiichi Sankyo webpage -
it doesn't seem that they think this could be
somehow important.

 

[gsgs]

Re: Antimicrob Agents Chemoter. CS-8958 (laninamivir prodrug), a long-acting neuraminidase inhibitor, shows superior anti-influenza virus activity after a single administration.

J Clin Pharmacol. 2010 Feb 9. [Epub ahead of print]

Clinical Pharmacokinetics of Laninamivir, a Novel Long-Acting Neuraminidase Inhibitor, After Single and Multiple Inhaled Doses of Its Prodrug, CS-8958, in Healthy Male Volunteers.
Ishizuka H, Yoshiba S, Okabe H, Yoshihara K.

Ltd.

Phase 1 studies of laninamivir, a novel long-acting neuraminidase inhibitor, were carried out to assess its safety, tolerability, and pharmacokinetics after inhaled administration of its prodrug, CS-8958. Healthy male volunteers (total N = 76) participated in double-blind, randomized, placebo-controlled trials and received 5, 10, 20, 40, 80, or 120 mg of a single dose or 20 or 40 mg of a twice-daily dose for 3 days. The clinical and laboratory parameters and plasma and urinary concentrations of CS-8958 and laninamivir for 144 hours post dosing were measured. There were no adverse events related to the test drug. CS-8958 disappeared from plasma with a half-life of about 2 hours, although laninamivir was slowly eliminated from the body, lasting for even up to 144 hours after administration with a half-life of about 3 days. Area under the curve and maximum concentration increased almost linearly with the dose administered. The cumulative urinary excretion amounts of CS-8958 and laninamivir were 2.3% to 3.6% and 10.7% to 14.6% of the dose, respectively. The half-life of the urinary excretion rates of laninamivir at higher single dose is comparable to plasma half-life. CS-8958, when inhaled by healthy volunteers, is well tolerated and exhibits a suitable pharmacokinetic profile, suggesting potential for long-lasting anti-influenza activity.

PMID: 20145259 [PubMed - as supplied by publisher]

 

[Shiloh]

Re: Antimicrob Agents Chemoter. CS-8958 (laninamivir prodrug), a long-acting neuraminidase inhibitor, shows superior anti-influenza virus activity after a single administration.

Source: http://www.eurekalert.org/pub_releases/2010-02/uow-ncf022510.php

Public release date: 25-Feb-2010

Contact: Yoshihiro Kawaoka
kawaokay@svm.vetmed.wisc.edu
608-265-4925
University of Wisconsin-Madison

Novel compound found effective against avian influenza virus

MADISON ? A novel compound is highly effective against the pathogenic H5N1 avian influenza virus, including some drug-resistant strains, according to new research led by a University of Wisconsin-Madison virologist.

The work, published in the Public Library of Science journal PLoS Pathogens on Feb. 26, suggests that the compound CS-8958 is a promising alternative antiviral for prevention and treatment of bird flu.

Antiviral drugs are a primary countermeasure against human influenza viruses, including the highly pathogenic H5N1 avian influenza virus, which causes bird flu. Emerging strains resistant to existing drugs, particularly oseltamivir (Tamiflu), pose a threat and make the development of alternate antivirals a pressing public health issue, says Yoshihiro Kawaoka, a professor of pathobiological sciences at the UW-Madison School of Veterinary Medicine and senior author of the new study.

Kawaoka and a group of researchers from Japan, Vietnam, and Indonesia tested a novel neuraminidase inhibitor R-125489 and its prodrug CS-8958, which had previously shown potent activity against seasonal influenza viruses in laboratory animals.

Working with mice, the researchers found that a single intranasal dose of CS-8958 given two hours after infection with H5N1 influenza virus resulted in a higher survival rate and lower virus levels than a standard five-day course of oseltamivir. CS-8958 was also effective against highly pathogenic and oseltamivir-resistant strains of H5N1 virus.

In addition to its therapeutic use, CS-8958 also protected mice against lethal H5N1 infection when given seven days before infection with the virus.

"This compound requires only a single administration for both treatment and prophylaxis. Such prophylaxis would be highly desirable for seasonal influenza as well as a potential pandemic situation," says Kawaoka.

Although follow-up studies will be needed to confirm the applicability of the findings to humans, "CS-8958 is highly effective for the treatment and prophylaxis of infection with H5N1 influenza viruses, including oseltamivir-resistant mutants," the authors conclude.

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Jill Sakai, 608-262-9772, jasakai@wisc.edu