This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Stone, J. A.
Right arrow Articles by Waldman, S. A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Stone, J. A.
Right arrow Articles by Waldman, S. A.

 Previous Article  |  Next Article 

Antimicrobial Agents and Chemotherapy, March 2002, p. 739-745, Vol. 46, No. 3
0066-4804/02/$04.00+0     DOI: 10.1128/AAC.46.3.739-745.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Single- and Multiple-Dose Pharmacokinetics of Caspofungin in Healthy Men

Julie A. Stone,1* Sherry D. Holland,1 Peter J. Wickersham,1 Andrew Sterrett,1 Michael Schwartz,1 Cynthia Bonfiglio,1 Michael Hesney,1 Gregory A. Winchell,1 Paul J. Deutsch,1 Howard Greenberg,2 Thomas L. Hunt,3 and Scott A. Waldman2

Merck Research Laboratories, West Point, Pennsylvania 19486,1 Thomas Jefferson University, Philadelphia, Pennsylvania 19107,2 Pharmaco International, Inc., Austin, Texas 787043

Received 5 April 2001/ Returned for modification 4 September 2001/ Accepted 15 November 2001

Caspofungin, a glucan synthesis inhibitor, is being developed as a parenteral antifungal agent. The pharmacokinetics of caspofungin following 1-h intravenous infusions in healthy men was investigated in four phase I studies. In an alternating two-panel (six men each), rising-single-dose study, plasma drug concentrations increased proportionally with the dose following infusions of 5 to 100 mg. The ß-phase half-life was 9 to 10 h. The plasma drug clearance rate averaged 10 to 12 ml/min. Renal clearance of unchanged drug was a minor pathway of elimination (~2% of the dose). Multiple-dose pharmacokinetics were investigated in a 2-week, serial-panel (5 or 6 men per panel) study of doses of 15, 35, and 70 mg administered daily; a 3-week, single-panel (10 men) study of a dose of 70 mg administered daily; and a parallel panel study (8 men) of a dose of 50 mg administered daily with or without a 70-mg loading dose on day 1. Moderate accumulation was observed with daily dosing. The degree of drug accumulation and the time to steady state were somewhat dose dependent. Accumulation averaged 24% at 15 mg daily and ~50% at 50 and 70 mg daily. Mean plasma drug concentrations were maintained above 1.0 µg/ml, a target selected to exceed the MIC at which 90% of the isolates of the most clinically relevant species of Candida were inhibited, throughout therapy with daily treatments of 70 or 50 mg plus the loading dose, while they fell below the target for the first 2 days of a daily treatment of 50 mg without the loading dose. Caspofungin infused intravenously as a single dose or as multiple doses was generally well tolerated. In conclusion, the pharmacokinetics of caspofungin supports the clinical evaluation of once-daily dosing regimens for efficacy against fungal infections.

* Corresponding author. Mailing address: WP75-100, Merck Research Laboratories, West Point, PA 19486. Phone: (215) 652-5705. Fax: (215) 993-3533. E-mail: julie_stone{at}merck.com.

Antimicrobial Agents and Chemotherapy, March 2002, p. 739-745, Vol. 46, No. 3
0066-4804/02/$04.00+0     DOI: 10.1128/AAC.46.3.739-745.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Canton, E., Peman, J., Valentin, A., Espinel-Ingroff, A., Gobernado, M. (2009). In Vitro Activities of Echinocandins against Candida krusei Determined by Three Methods: MIC and Minimal Fungicidal Concentration Measurements and Time-Kill Studies. Antimicrob. Agents Chemother. 53: 3108-3111 [Abstract] [Full Text]  
  • Spriet, I., Annaert, P., Meersseman, P., Hermans, G., Meersseman, W., Verbesselt, R., Willems, L. (2009). Pharmacokinetics of caspofungin and voriconazole in critically ill patients during extracorporeal membrane oxygenation. J Antimicrob Chemother 63: 767-770 [Abstract] [Full Text]  
  • Saez-Llorens, X., Macias, M., Maiya, P., Pineros, J., Jafri, H. S., Chatterjee, A., Ruiz, G., Raghavan, J., Bradshaw, S. K., Kartsonis, N. A., Sun, P., Strohmaier, K. M., Fallon, M., Bi, S., Stone, J. A., Chow, J. W. (2009). Pharmacokinetics and Safety of Caspofungin in Neonates and Infants Less than 3 Months of Age. Antimicrob. Agents Chemother. 53: 869-875 [Abstract] [Full Text]  
  • Andes, D., Pascual, A., Marchetti, O. (2009). Antifungal Therapeutic Drug Monitoring: Established and Emerging Indications. Antimicrob. Agents Chemother. 53: 24-34 [Full Text]  
  • van de Sande, W. W. J., van Vianen, W., ten Kate, M. T., Vissers, J., Laurijsens, J., Tavakol, M., Rijnders, B. J. A., Mathot, R. A. A., Bakker-Woudenberg, I. A. J. M. (2008). Caspofungin Prolongs Survival of Transiently Neutropenic Rats with Advanced-Stage Invasive Pulmonary Aspergillosis. Antimicrob. Agents Chemother. 52: 1345-1350 [Abstract] [Full Text]  
  • Castagnola, E., Cappelli, B., Faraci, M., Fallani, S., Cassetta, M. I., Novelli, A. (2007). Maintenance of Therapeutic Concentrations of Caspofungin after Temporary Treatment Interruption (48 Hours) in a Child with Invasive Aspergillosis. Antimicrob. Agents Chemother. 51: 3775-3775 [Full Text]  
  • Mistry, G. C., Migoya, E., Deutsch, P. J., Winchell, G., Hesney, M., Li, S., Bi, S., Dilzer, S., Lasseter, K. C., Stone, J. A. (2007). Single- and Multiple-Dose Administration of Caspofungin in Patients With Hepatic Insufficiency: Implications for Safety and Dosing Recommendations. J Clin Pharmacol 47: 951-961 [Abstract] [Full Text]  
  • Nguyen, T. H., Hoppe-Tichy, T., Geiss, H. K., Rastall, A. C., Swoboda, S., Schmidt, J., Weigand, M. A. (2007). Factors influencing caspofungin plasma concentrations in patients of a surgical intensive care unit. J Antimicrob Chemother 60: 100-106 [Abstract] [Full Text]  
  • da Matta, V. L. R., Melhem, M. d. S. C., Colombo, A. L., Moretti, M. L., Rodero, L., de Almeida, G. M. D., Martins, M. d. A., Costa, S. F., Souza Dias, M. B. G., Nucci, M., Levin, A. S. (2007). Antifungal Drug Susceptibility Profile of Pichia anomala Isolates from Patients Presenting with Nosocomial Fungemia. Antimicrob. Agents Chemother. 51: 1573-1576 [Abstract] [Full Text]  
  • Antachopoulos, C., Meletiadis, J., Sein, T., Roilides, E., Walsh, T. J. (2007). Concentration-Dependent Effects of Caspofungin on the Metabolic Activity of Aspergillus Species. Antimicrob. Agents Chemother. 51: 881-887 [Abstract] [Full Text]  
  • Cota, J., Carden, M., Graybill, J. R., Najvar, L. K., Burgess, D. S., Wiederhold, N. P. (2006). In Vitro Pharmacodynamics of Anidulafungin and Caspofungin against Candida glabrata Isolates, Including Strains with Decreased Caspofungin Susceptibility. Antimicrob. Agents Chemother. 50: 3926-3928 [Abstract] [Full Text]  
  • Morris, M. I., Villmann, M. (2006). Echinocandins in the management of invasive fungal infections, part 1.. Am J Health Syst Pharm 63: 1693-1703 [Abstract] [Full Text]  
  • van Vianen, W., de Marie, S., ten Kate, M. T., Mathot, R. A. A., Bakker-Woudenberg, I. A. J. M. (2006). Caspofungin: antifungal activity in vitro, pharmacokinetics, and effects on fungal load and animal survival in neutropenic rats with invasive pulmonary aspergillosis. J Antimicrob Chemother 57: 732-740 [Abstract] [Full Text]  
  • Groll, A. H., Attarbaschi, A., Schuster, F. R., Herzog, N., Grigull, L., Dworzak, M. N., Beutel, K., Laws, H.-J., Lehrnbecher, T. (2006). Treatment with caspofungin in immunocompromised paediatric patients: a multicentre survey. J Antimicrob Chemother 57: 527-535 [Abstract] [Full Text]  
  • Wiederhold, N. P., Kontoyiannis, D. P., Prince, R. A., Lewis, R. E. (2005). Attenuation of the Activity of Caspofungin at High Concentrations against Candida albicans: Possible Role of Cell Wall Integrity and Calcineurin Pathways. Antimicrob. Agents Chemother. 49: 5146-5148 [Abstract] [Full Text]  
  • Walsh, T. J., Adamson, P. C., Seibel, N. L., Flynn, P. M., Neely, M. N., Schwartz, C., Shad, A., Kaplan, S. L., Roden, M. M., Stone, J. A., Miller, A., Bradshaw, S. K., Li, S. X., Sable, C. A., Kartsonis, N. A. (2005). Pharmacokinetics, Safety, and Tolerability of Caspofungin in Children and Adolescents. Antimicrob. Agents Chemother. 49: 4536-4545 [Abstract] [Full Text]  
  • Wegner, B., Baer, P., Gauer, S., Oremek, G., Hauser, I. A., Geiger, H. (2005). Caspofungin is less nephrotoxic than amphotericin B in vitro and predominantly damages distal renal tubular cells. Nephrol Dial Transplant 20: 2071-2079 [Abstract] [Full Text]  
  • Cocuaud, C., Rodier, M.-H., Daniault, G., Imbert, C. (2005). Anti-metabolic activity of caspofungin against Candida albicans and Candida parapsilosis biofilms. J Antimicrob Chemother 56: 507-512 [Abstract] [Full Text]  
  • Sandhu, P., Lee, W., Xu, X., Leake, B. F., Yamazaki, M., Stone, J. A., Lin, J. H., Pearson, P. G., Kim, R. B. (2005). HEPATIC UPTAKE OF THE NOVEL ANTIFUNGAL AGENT CASPOFUNGIN. Drug Metab. Dispos. 33: 676-682 [Abstract] [Full Text]  
  • Mukherjee, P. K., Sheehan, D. J., Hitchcock, C. A., Ghannoum, M. A. (2005). Combination Treatment of Invasive Fungal Infections. Clin. Microbiol. Rev. 18: 163-194 [Abstract] [Full Text]  
  • Messer, S. A., Kirby, J. T., Sader, H. S., Fritsche, T. R., Jones, R. N. (2004). Initial results from a longitudinal international surveillance programme for anidulafungin (2003). J Antimicrob Chemother 54: 1051-1056 [Abstract] [Full Text]  
  • Wong, H., Grossman, S. J., Bai, S. A., Diamond, S., Wright, M. R., Grace, J. E. Jr., Qian, M., He, K., Yeleswaram, K., Christ, D. D. (2004). THE CHIMPANZEE (PAN TROGLODYTES) AS A PHARMACOKINETIC MODEL FOR SELECTION OF DRUG CANDIDATES: MODEL CHARACTERIZATION AND APPLICATION. Drug Metab. Dispos. 32: 1359-1369 [Abstract] [Full Text]  
  • Stone, J. A., Migoya, E. M., Hickey, L., Winchell, G. A., Deutsch, P. J., Ghosh, K., Freeman, A., Bi, S., Desai, R., Dilzer, S. C., Lasseter, K. C., Kraft, W. K., Greenberg, H., Waldman, S. A. (2004). Potential for Interactions between Caspofungin and Nelfinavir or Rifampin. Antimicrob. Agents Chemother. 48: 4306-4314 [Abstract] [Full Text]  
  • Sandhu, P., Xu, X., Bondiskey, P. J., Balani, S. K., Morris, M. L., Tang, Y. S., Miller, A. R., Pearson, P. G. (2004). Disposition of Caspofungin, a Novel Antifungal Agent, in Mice, Rats, Rabbits, and Monkeys. Antimicrob. Agents Chemother. 48: 1272-1280 [Abstract] [Full Text]  
  • Stone, J. A., Xu, X., Winchell, G. A., Deutsch, P. J., Pearson, P. G., Migoya, E. M., Mistry, G. C., Xi, L., Miller, A., Sandhu, P., Singh, R., deLuna, F., Dilzer, S. C., Lasseter, K. C. (2004). Disposition of Caspofungin: Role of Distribution in Determining Pharmacokinetics in Plasma. Antimicrob. Agents Chemother. 48: 815-823 [Abstract] [Full Text]  
  • Dannaoui, E., Lortholary, O., Dromer, F. (2004). In Vitro Evaluation of Double and Triple Combinations of Antifungal Drugs against Aspergillus fumigatus and Aspergillus terreus. Antimicrob. Agents Chemother. 48: 970-978 [Abstract] [Full Text]  
  • Pfaller, M. A., Messer, S. A., Boyken, L., Rice, C., Tendolkar, S., Hollis, R. J., Diekema, D. J. (2003). Caspofungin Activity against Clinical Isolates of Fluconazole-Resistant Candida. J. Clin. Microbiol. 41: 5729-5731 [Abstract] [Full Text]  
  • Madariaga, M. G., Tenorio, A., Proia, L. (2003). Trichosporon inkin Peritonitis Treated with Caspofungin. J. Clin. Microbiol. 41: 5827-5829 [Abstract] [Full Text]  
  • Schwarz, P., Dromer, F., Lortholary, O., Dannaoui, E. (2003). In Vitro Interaction of Flucytosine with Conventional and New Antifungals against Cryptococcus neoformans Clinical Isolates. Antimicrob. Agents Chemother. 47: 3361-3364 [Abstract] [Full Text]  
  • Pfaller, M. A., Diekema, D. J., Messer, S. A., Hollis, R. J., Jones, R. N. (2003). In Vitro Activities of Caspofungin Compared with Those of Fluconazole and Itraconazole against 3,959 Clinical Isolates of Candida spp., Including 157 Fluconazole-Resistant Isolates. Antimicrob. Agents Chemother. 47: 1068-1071 [Abstract] [Full Text]  
  • Letscher-Bru, V., Herbrecht, R. (2003). Caspofungin: the first representative of a new antifungal class. J Antimicrob Chemother 51: 513-521 [Abstract] [Full Text]  
  • Bachmann, S. P., VandeWalle, K., Ramage, G., Patterson, T. F., Wickes, B. L., Graybill, J. R., Lopez-Ribot, J. L. (2002). In Vitro Activity of Caspofungin against Candida albicans Biofilms. Antimicrob. Agents Chemother. 46: 3591-3596 [Abstract] [Full Text]  
  • Ramage, G., VandeWalle, K., Bachmann, S. P., Wickes, B. L., Lopez-Ribot, J. L. (2002). In Vitro Pharmacodynamic Properties of Three Antifungal Agents against Preformed Candida albicans Biofilms Determined by Time-Kill Studies. Antimicrob. Agents Chemother. 46: 3634-3636 [Abstract] [Full Text]  
  • (2002). Pharmacokinetics of Caspofungin. JWatch Infect. Diseases 2002: 15-15 [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»