Skip NavigationSkip to Content
Return Return to Search Results

Efficacy, plasma pharmacokinetics, and safety of icofungipen, an inhibitor of Candida isoleucyl-tRNA synthetase, in treatment of experimental disseminated candidiasis in persistently neutropenic rabbits

  1. Author:
    Petraitiene, R.
    Petraitis, V.
    Kelaher, A. M.
    Sarafandi, A. A.
    Mickiene, D.
    Groll, A. H.
    Sein, T.
    Bacher, J.
    Walsh, T. J.

  2. Author Address

    NCI, Pediat Oncol Branch, Immunocompromised Host Sect, NIH, Bethesda, MD 20892 USA. SAIC Frederick Inc, Frederick, MD USA. NIH, Off Res Serv, Vet Resources Program, Bethesda, MD USA. Univ Chicago Hosp, Dept Pediat Hematol Oncol, Munster, Germany Walsh, TJ, NCI, Pediat Oncol Branch, Immunocompromised Host Sect, NIH, Bldg 10,CRC,Rm 1W-5740,10 Ctr Dr,MSC 1100, Bethesda, MD 20892 USA
    1. Year: 2005
    2. Date: MAY
  2. Journal: Antimicrobial Agents and Chemotherapy
    1. 49
    2. 5
    3. Pages: 2084-2092
  4. Type of Article: Article
  1. Abstract:

    Icofungipen (formerly PLD-118) is a synthetic derivative of the naturally occurring P-amino acid cispentacin that blocks isoleucyl-tRNA synthetase, resulting in the inhibition of protein synthesis and growth of fungal cells. We investigated the efficacy, plasma pharmacokinetics, and safety of icofungipen in escalating dosages for the treatment of experimental subacute disseminated candidiasis in persistently neutropenic rabbits. Icofungipen was administered for 10 days starting 24 h after the intravenous inoculation of 10(3) Candida albicans blastoconidia. Study groups consisted of rabbits treated with icofungipen at 4 (ICO-4), 10 (ICO-10), and 25 (ICO-25) mg/kg of body weight/day in two divided dosages, rabbits treated with fluconazole at 10 mg/kg/day, rabbits treated with amphotericin B at I mg/kg/day, and untreated controls. Levels of icofungipen in plasma were derivatized by phthaldialdehyde and quantified by high-performance liquid chromatography with fluorescence detection. Rabbits treated with ICO-10 (P < 0.01) and ICO-25 (P < 0.001) showed significant dosage-dependent tissue clearance of C. albicans from the liver, spleen, kidney, brain, vitreous, vena cava, and lung in comparison to untreated controls. ICO-25 cleared C. albicans from all tissues and had activity comparable to that of amphotericin B versus untreated controls (P < 0.001). Pharmacokinetics of icofungipen in plasma approximated a dose-dependent relationship of the maximum concentration of drug in serum and the area under the concentration-time curve. There was no significant elevation of the levels of hepatic transaminases, alkaline phosphatase, bilirubin, urea nitrogen, or creatinine in icofungipen-treated rabbits. Icofungipen followed dose-dependent pharmacokinetics and was effective in the treatment of experimental disseminated candidiasis, including central nervous system infection, in persistently neutropenic rabbits

    See More

  1. Keywords:

External Sources

  1. View record in Web of Science®
  2. WOS: 000228982600055

Library Notes

  1. No notes added.
NCI at Frederick

You are leaving a government website.

This external link provides additional information that is consistent with the intended purpose of this site. The government cannot attest to the accuracy of a non-federal site.

Linking to a non-federal site does not constitute an endorsement by this institution or any of its employees of the sponsors or the information and products presented on the site. You will be subject to the destination site's privacy policy when you follow the link.

ContinueCancel