Affiliation:
1. Department of Pharmacy Services, Oregon Health & Science University, 3181 SW Sam Jackson Park Road, CR9-4, Portland, Oregon 97239
2. Department of Pharmacy Practice, Oregon State University/Oregon Health & Science University College of Pharmacy, 3303 SW Bond Avenue, CH12C, Portland, Oregon 97239
3. Bone Marrow Transplant Program, Oregon Health & Science University, 3181 SW Sam Jackson Park Road, Portland, Oregon 97239
Abstract
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
. 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 (
C
max
) 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
C
max
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
C
max
/MIC and AUC from time zero to 24 h (AUC
0-24
)/MIC ratios for a bacteriostatic effect against
Streptococcus pneumoniae
. Twenty-seven patients (93%) achieved a
C
max
/MIC ratio for a bacteriostatic effect against
S. aureus
, and 28 patients (97%) achieved an AUC
0-24
/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.
Publisher
American Society for Microbiology
Subject
Infectious Diseases,Pharmacology (medical),Pharmacology