Pharmacokinetics, serum inhibitory and bactericidal activity, and safety of telavancin in healthy subjects.
The pharmacokinetics, tolerability, and serum inhibitory and bactericidal titers of telavancin, a new rapidly bactericidal lipoglycopeptide with multiple mechanisms of action against gram-positive pathogens, were assessed in a two-part, randomized, double-blind, placebo-controlled, ascending-dose study with 54 healthy men. In part 1, single ascending intravenous doses of 0.25 to 15 mg/kg of body weight were studied. In part 2, multiple ascending doses (30-min infusions of 7.5 to 15 mg/kg/day) were studied over 7 days. Following the administration of multiple doses, steady state was achieved by days 3 to 4. At day 7 after the administration of telavancin at 7.5, 12.5, and 15 mg/kg/day, peak concentrations in plasma were 96.7, 151.3, and 202.5 microg/ml, respectively, and steady-state area-under-the-curve values were 700, 1,033, and 1,165 microg x h/ml, respectively. The elimination half-life ranged from 6.9 to 9.1 h following the administration of doses > or =5 mg/kg. Most adverse events were mild in severity. At 24 h postinfusion, serum from subjects given telavancin demonstrated potent bactericidal activity against methicillin-resistant Staphylococcus aureus and penicillin-resistant Streptococcus pneumoniae strains. The results suggest that telavancin may be an effective once-daily therapy for serious bacterial infections caused by these pathogens.
Shaw
J P
JP
Theravance, Inc., 901 Gateway Blvd., South San Francisco, CA 94080, USA. jpshaw@theravance.com
Seroogy
J
J
Kaniga
K
K
Higgins
D L
DL
Kitt
M
M
Barriere
S
S
D000293:Adolescent; D000328:Adult; D000617:Aminoglycosides / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D019540:Area Under Curve; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D006207:Half-Life; D006801:Humans; D007275:Injections, Intravenous; D000077427:Lipoglycopeptides; D008297:Male; D016106:Methicillin Resistance; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D015610:Serum Bactericidal Test; D013211:Staphylococcus aureus / Q000187:drug effects; D013296:Streptococcus pneumoniae / Q000187:drug effects
D000617:Aminoglycosides; D000900:Anti-Bacterial Agents; D000077427:Lipoglycopeptides; C487637:telavancin