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Antimicrob. Agents Chemother. doi:10.1128/AAC.00943-08
Copyright (c) 2008, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Daptomycin Pharmacokinetics in Adult Oncology Patients with Neutropenic Fever

Oncology Clinical Pharmacy Specialist, Oregon Health & Science University, Department of Pharmacy Services, 3181 SW Sam Jackson Park Road, CR9-4, Portland, OR 97239; Oregon State University/Oregon Health & Science University College of Pharmacy, Department of Pharmacy Practice, 3303 SW Bond Avenue, CH12C, Portland, OR 97239; Oregon Health & Science University, Bone Marrow Transplant Program, 3181 SW Sam Jackson Park Road, L586, Portland, OR 97239; Oregon Health & Science University, Bone Marrow Transplant Program, 3181 SW Sam Jackson Park Road, UHN73C, Portland, OR 97239

^* To whom correspondence should be addressed. Email: munarm{at}ohsu.edu.

	Abstract

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. Daptomycin pharmacokinetics 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 hours after the initial 6 mg/kg daptomycin IV infusion. Daptomycin total and free plasma concentrations were determined by HPLC. Concentration-time data were analyzed by noncompartmental methods. Results (mean ± S.D.; range): C_max (49.04 ± 12.42 µg/mL; 21.54 - 75.20), C₂₄ (6.48 ± 5.31 µg/mL; 1.48 - 29.26), AUC_0- (521.37 ± 523.53 µg*hr/mL; 164.64 - 3155.11), V_SS (0.18 ± 0.05 L/kg; 0.13-0.36), CL (15.04 ± 6.09 mL/hr/kg; 1.90-34.76), T_1/2 (11.34 ± 14.15 hr; 5.17 - 83.92), MRT (15.67 ± 20.66 hr; 7.00-121.73), T_max (median=0.6; 0.5-2.5). Fraction unbound in the plasma (f_u) was 0.06 ± 0.02. All patients achieved C_max/MIC and AUC_0-24/MIC for a bacteriostatic effect against S. pneumoniae. Twenty-seven patients (93%) achieved C_max/MIC and 28 patients (97%) achieved AUC_0-24/MIC for a bacteriostatic effect against S. aureus. Free plasma daptomycin concentrations were above the MIC for 50 - 100% of the dosing interval in 100% of patients for S. pneumoniae and 90% of patients for S. aureus. Median time to defervescence was 3 days from the start of daptomycin therapy. In summary, a 6 mg/kg IV of daptomycin every 24 hours was effective and well tolerated in neutropenic cancer patients.