Compartmental pharmacokinetics of the antifungal echinocandin caspofungin (MK-0991) in rabbits

A. H. Groll, B. M. Gullick, R. Petraitiene, V. Petraitis, M. Candelario, S. C. Piscitelli, T. J. Walsh

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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 increased Vdss, 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.

Original languageEnglish (US)
Pages (from-to)596-600
Number of pages5
JournalAntimicrobial Agents and Chemotherapy
Volume45
Issue number2
DOIs
Publication statusPublished - 2001
Externally publishedYes

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ASJC Scopus subject areas

  • Pharmacology (medical)

Cite this

Groll, A. H., Gullick, B. M., Petraitiene, R., Petraitis, V., Candelario, M., Piscitelli, S. C., & Walsh, T. J. (2001). Compartmental pharmacokinetics of the antifungal echinocandin caspofungin (MK-0991) in rabbits. Antimicrobial Agents and Chemotherapy, 45(2), 596-600. https://doi.org/10.1128/AAC.45.2.596-600.2001