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| |  Cancer Patients With Neutropenia Respond to Daptomycin Treatment: Presented at ACCP By Crina Frincu-Mallos, PhD PHILADELPHIA -- September 21, 2008 -- Daptomycin is effective and well tolerated in neutropenic cancer patients, according to trial data reported here at the American College of Clinical Pharmacology (ACCP) 37th Annual Meeting. "Daptomycin is the first antibacterial agent of the cyclic lipopeptides [class] with in vitro bactericidal activity against gram-positive organisms," said study investigator Myrna Y. Munar, PharmD, Oregon State University/Oregon Health & Science University College of Pharmacy, Portland, Oregon, in a poster presentation on September 14. Daptomycin showed activity where other antibacterials failed due to drug resistance, such as against vancomycin-resistant Enterococci, methicillin-resistant Staphylococci, and glycopeptide-resistant Staphylococcus aureus, according to the researchers. The investigators evaluated the pharmacokinetics and pharmacodynamics of daptomycin in 29 adult oncology patients presenting with neutropenic fever. Following an intravenous infusion of daptomycin 6 mg/kg, blood samples were drawn from all patients at 0, 0.5, 1, 2, 4, 8, 12, and 24 hours. Total and free plasma concentrations were determined using high-performance liquid chromatography. Concentration data were plotted versus time and analysed by noncompartmental methods. Maximum plasma concentration (Cmax) relative to the minimum inhibitory concentration (MIC) of the pathogen (i.e., Cmax/MIC), together with the area under the curve (AUC) that is above the bacterial MIC during the dosage interval (i.e., AUC0-24/MIC in this case) are major determinants of clinical efficacy, explained the investigators. The mean value for Cmax was 49.04 mcg/mL (range, 21.54-75.20 mcg/mL) and Tmax was a median of 0.6 hours (range, 0.5-2.5 hrs). At 24 hours after treatment with daptomycin, the plasma concentration of the drug was 6.48 mcg/mL (range, 1.48-29.26 mcg/mL) and AUC concentration time curve was 521.37 mcghr/mL (range, 164.64-3155.11 mcghr/mL). Renal clearance (CL) was 15.04 mL/hr/kg (range, 1.90-34.76 mL/hr/kg). The values for Cmax/MIC and AUC0-24/MIC indicate that all patients achieved a bacteriostatic effect against S. pneumoniae. Furthermore, 93% of 27 patients with febrile neutropenia achieved Cmax/MIC, indicating a bacteriostatic effect against S. aureus. In 97% of the patients, values for AUC0-24/MIC indicate that they achieved a bacteriostatic effect against S. aureus, according to Dr. Munar. Free plasma concentrations of daptomycin were above the MIC for 50% to 100% of the dosing interval, in all patients for S. pneumoniae and in 90% of the patients for S. aureus, noted the investigators. Dr. Munar said the mean time to defervescence was 3 days from the start of daptomycin treatment. [Presentation title: Daptomycin PK and PD in Adult Oncology Patients With Neutropenic Fever. Abstract 25]
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