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Pharmacology

Compartmental Pharmacokinetics of the Antifungal Echinocandin Caspofungin (MK-0991) in Rabbits

Andreas H. Groll, Bryan M. Gullick, Ruta Petraitiene, Vidmantas Petraitis, Myrna Candelario, Stephen C. Piscitelli, Thomas J. Walsh
Andreas H. Groll
Immunocompromised Host Section, Pediatric Oncology Branch, National Cancer Institute,and
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Bryan M. Gullick
Immunocompromised Host Section, Pediatric Oncology Branch, National Cancer Institute,and
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Ruta Petraitiene
Immunocompromised Host Section, Pediatric Oncology Branch, National Cancer Institute,and
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Vidmantas Petraitis
Immunocompromised Host Section, Pediatric Oncology Branch, National Cancer Institute,and
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Myrna Candelario
Immunocompromised Host Section, Pediatric Oncology Branch, National Cancer Institute,and
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Stephen C. Piscitelli
Pharmacokinetics Research Laboratory, Pharmacy Department, Warren Grant Magnuson Clinical Center, National Institutes of Health, Bethesda, Maryland 20892
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Thomas J. Walsh
Immunocompromised Host Section, Pediatric Oncology Branch, National Cancer Institute,and
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DOI: 10.1128/AAC.45.2.596-600.2001
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ABSTRACT

The pharmacokinetics of the antifungal echinocandin-lipopeptide caspofungin (MK-0991) in plasma were studied in groups of three healthy rabbits after single and multiple daily intravenous administration of doses of 1, 3, and 6 mg/kg of body weight. Concentrations were measured by a validated high-performance liquid chromatography method and fitted into a three-compartment open pharmacokinetic model. Across the investigated dosage range, caspofungin displayed dose-independent pharmacokinetics. Following administration over 7 days, the mean peak concentration in plasma (Cmax) ± standard error of the mean increased from 16.01 ± 0.61 μg/ml at the 1-mg/kg dose to 105.52 ± 8.92 μg/ml at the 6-mg/kg dose; the mean area under the curve from 0 h to infinity rose from 13.15 ± 2.37 to 158.43 ± 15.58 μg · h/ml, respectively. The mean apparent volume of distribution at steady state (Vdss) was 0.299 ± 0.011 liter/kg at the 1-mg/kg dose and 0.351 ± 0.016 liter/kg at the 6-mg/kg dose (not significant [NS]). Clearance (CL) ranged from 0.086 ± 0.017 liter/kg/h at the 1-mg/kg dose to 0.043 ± 0.004 liter/kg/h at the 6-mg/kg dose (NS), and the mean terminal half-life was between 30 and 34 h (NS). Except for a trend towards an increasedVdss, there were no significant differences in pharmacokinetic parameters in comparison to those after single-dose administration. Caspofungin was well tolerated, displayed linear pharmacokinetics that fit into a three-compartment pharmacokinetic model, and achieved sustained concentrations in plasma that were multiple times in excess of reported MICs for susceptible opportunistic fungi.

  • Copyright © 2001 American Society for Microbiology
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Compartmental Pharmacokinetics of the Antifungal Echinocandin Caspofungin (MK-0991) in Rabbits
Andreas H. Groll, Bryan M. Gullick, Ruta Petraitiene, Vidmantas Petraitis, Myrna Candelario, Stephen C. Piscitelli, Thomas J. Walsh
Antimicrobial Agents and Chemotherapy Feb 2001, 45 (2) 596-600; DOI: 10.1128/AAC.45.2.596-600.2001

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Compartmental Pharmacokinetics of the Antifungal Echinocandin Caspofungin (MK-0991) in Rabbits
Andreas H. Groll, Bryan M. Gullick, Ruta Petraitiene, Vidmantas Petraitis, Myrna Candelario, Stephen C. Piscitelli, Thomas J. Walsh
Antimicrobial Agents and Chemotherapy Feb 2001, 45 (2) 596-600; DOI: 10.1128/AAC.45.2.596-600.2001
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KEYWORDS

Anti-Bacterial Agents
antifungal agents
peptides
Peptides, Cyclic

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