Moderate liver impairment has no influence on daptomycin pharmacokinetics

• Published in: Journal of clinical pharmacology Vol. 44; no. 7; p. 715
• Main Author: Dvorchik, Barry
• Format: Journal Article
• Language: English
• Published: England 01.07.2004
• Subjects: Adult; Aged; Anti-Bacterial Agents - adverse effects; Anti-Bacterial Agents - pharmacokinetics; Area Under Curve; Daptomycin - adverse effects; Daptomycin - pharmacokinetics; Female; Half-Life; Humans; Liver Diseases - complications; Liver Diseases - metabolism; Male; Metabolic Clearance Rate; Middle Aged
• ISSN: 0091-2700
• DOI: 10.1177/0091270004266619

Daptomycin (N-decanoyl-L-tryptophyl-L-asparaginyl-L-aspartyl-L-threonylglycyl-L-ornithyl-L-aspartyl-D-alanyl-L-aspartylglycyl-D-seryl-threo-3-methyl-L-glutamyl-3-anthraniloyl-L-alanine-lactone) is a novel cyclic lipopeptide antibiotic derived from the fermentation of Streptomyces roseosporus. Daptomycin was recently approved for the treatment of complicated skin and skin structure infections caused by aerobic gram-positive bacteria, including those caused by methicillin-resistant and methicillin-susceptible Staphylococcus aureus. This single-dose, parallel-design, matched-controlled study was designed to evaluate the pharmacokinetics of daptomycin in subjects between ages 18 and 80 years with moderately impaired hepatic function (Child-Pugh Class B, n = 10). Subjects were administered a single intravenous dose (6 mg/kg total body weight) over 30 minutes using a syringe pump. A normal volunteer control group matched by weight (+/-25 lb/11 kg), age (+/-10 years), and sex was included in this study for comparison to the hepatic-impaired group. The pharmacokinetic parameters of daptomycin were similar in both groups. Adverse events occurred only in the hepatic-impaired patients and were consistent with the subjects' disease state. In conclusion, subjects with moderate hepatic impairment receiving daptomycin do not require an adjustment in daptomycin dose or dose regimen.