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Antimicrobial Agents and Chemotherapy, February 2009, p. 428-434, Vol. 53, No. 2
0066-4804/09/$08.00+0 doi:10.1128/AAC.00943-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.
Daptomycin Pharmacokinetics in Adult Oncology Patients with Neutropenic Fever 
Joseph S. Bubalo,1
Myrna Y. Munar,2*
Ganesh Cherala,2
Brandon Hayes-Lattin,3 and
Richard Maziarz3
Department of Pharmacy Services, Oregon Health & Science University, 3181 SW Sam Jackson Park Road, CR9-4, Portland, Oregon 97239,1 Department of Pharmacy Practice, Oregon State University/Oregon Health & Science University College of Pharmacy, 3303 SW Bond Avenue, CH12C, Portland, Oregon 97239,2 Bone Marrow Transplant Program, Oregon Health & Science University, 3181 SW Sam Jackson Park Road, Portland, Oregon 972393
Received 16 July 2008/ Returned for modification 18 October 2008/ Accepted 11 November 2008
Daptomycin is the first antibacterial agent of the cyclic lipopeptides with in vitro bactericidal activity against gram-positive organisms, including vancomycin-resistant enterococci, methicillin-resistant staphylococci, and glycopeptide-resistant Staphylococcus aureus. The pharmacokinetics of daptomycin were determined in 29 adult oncology patients with neutropenic fever. Serial blood samples were drawn at 0, 0.5, 1, 2, 4, 8, 12, and 24 h after the initial intravenous infusion of 6 mg/kg of body weight daptomycin. Daptomycin total and free plasma concentrations were determined by high-pressure liquid chromatography. Concentration-time data were analyzed by noncompartmental methods. The results (presented as means ± standard deviations and ranges, unless indicated otherwise) were as follows: the maximum concentration of drug in plasma (Cmax) was 49.04 ± 12.42 µg/ml (range, 21.54 to 75.20 µg/ml), the 24-h plasma concentration was 6.48 ± 5.31 µg/ml (range, 1.48 to 29.26 µg/ml), the area under the concentration-time curve (AUC) from time zero to infinity was 521.37 ± 523.53 µg·h/ml (range, 164.64 to 3155.11 µg·h/ml), the volume of distribution at steady state was 0.18 ± 0.05 liters/kg (range, 0.13 to 0.36 liters/kg), the clearance was 15.04 ± 6.09 ml/h/kg (range, 1.90 to 34.76 ml/h/kg), the half-life was 11.34 ± 14.15 h (range, 5.17 to 83.92 h), the mean residence time was 15.67 ± 20.66 h (range, 7.00 to 121.73 h), and the median time to Cmax was 0.6 h (range, 0.5 to 2.5 h). The fraction unbound in the plasma was 0.06 ± 0.02. All patients achieved Cmax/MIC and AUC from time zero to 24 h (AUC0-24)/MIC ratios for a bacteriostatic effect against Streptococcus pneumoniae. Twenty-seven patients (93%) achieved a Cmax/MIC ratio for a bacteriostatic effect against S. aureus, and 28 patients (97%) achieved an AUC0-24/MIC ratio for a bacteriostatic effect against S. aureus. Free plasma daptomycin concentrations were above the MIC for 50 to 100% of the dosing interval in 100% of patients for S. pneumoniae and 90% of patients for S. aureus. The median time to defervescence was 3 days from the start of daptomycin therapy. In summary, a 6-mg/kg intravenous infusion of daptomycin every 24 h was effective and well tolerated in neutropenic cancer patients.
* Corresponding author. Mailing address: Department of Pharmacy Practice, Oregon State University/Oregon Health & Science University College of Pharmacy, 3303 SW Bond Avenue, CH12C, Portland, OR 97239. Phone: (503) 494-5164. Fax: (503) 494-8797. E-mail: munarm{at}ohsu.edu
Published ahead of print on 17 November 2008.
Antimicrobial Agents and Chemotherapy, February 2009, p. 428-434, Vol. 53, No. 2
0066-4804/09/$08.00+0 doi:10.1128/AAC.00943-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.
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