The pharmacokinetics, tissue penetration and in-vitro activity of loracarbef, a beta-lactam antibiotic of the carbacephem class.
The pharmacokinetics of loracarbef in plasma and a mild inflammatory exudate were studied in human volunteers. After a single oral dose of 400 mg, a mean maximum drug concentration (Cmax) of 17.8 mg/L was achieved in the plasma at 1.2 h (mean Tmax). The mean plasma elimination half-life (T1/2) was 1.3 h. In the inflammatory exudate the mean Cmax was 8.9 mg/L at a mean Tmax of 2.0 h and with a mean T1/2 of 1.7 h. The mean penetration into the inflammatory exudate was 90.1%. The in-vitro activity of loracarbef was determined against Haemophilus influenzae and Moraxella catarrhalis (MIC90s of 4 mg/L and 1 mg/L respectively, regardless of beta-lactamase production), as well as Streptococcus pneumoniae (MIC90 of 2 mg/L). Loracarbef was also active against Escherichia coli, Proteus mirabilis and Klebsiella pneumoniae (MIC90s of < or = 2 mg/L). The in-vitro activity and pharmacokinetics of loracarbef suggest that it would be efficative therapy for patients with community-acquired respiratory and urinary tract infections caused by the most frequently-encountered bacterial pathogens.
Lees
A S
AS
Department of Microbiology, Dudley Road Hospital, Birmingham, UK.
Andrews
J M
JM
Wise
R
R
D000328:Adult; D000658:Amoxicillin / Q000494:pharmacology; D019980:Amoxicillin-Potassium Clavulanate Combination; D002433:Cefaclor / Q000494:pharmacology; D002511:Cephalosporins / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology; D002969:Clavulanic Acids / Q000494:pharmacology; D004359:Drug Therapy, Combination / Q000494:pharmacology; D004755:Enterobacteriaceae / Q000187:drug effects; D005122:Exudates and Transudates / Q000378:metabolism*; D006193:Haemophilus influenzae / Q000187:drug effects; D006207:Half-Life; D006801:Humans; D008297:Male; D008826:Microbial Sensitivity Tests; D001936:Moraxella catarrhalis / Q000187:drug effects; D013211:Staphylococcus aureus / Q000187:drug effects; D013296:Streptococcus pneumoniae / Q000187:drug effects
D002511:Cephalosporins; D002969:Clavulanic Acids; C054920:loracarbef; D002433:Cefaclor; D019980:Amoxicillin-Potassium Clavulanate Combination; D000658:Amoxicillin