Biological Activity
clinafloxacin is a broad-spectrum antibiotic of the quinolone carboxylic acid category that inhibits both dna gyrase and topoisomerase iv dually in streptococcus pneumonia. clinafloxacin, a fluoroquinolone, is currently in development for oral and intravenous therapy of serious infections.in selected volunteer subjects and patients, after the administration of oral and intravenous doses of racemic drug, the clinafloxacin showed a broad-spectrum antibiotic of the quinolone carboxylic acid category. the absorption of the clinafloxacin enantiomer was rapid after oral 400 mg dose and 400 mg intravenous dose of racemic drug [1]. clinafloxacin showed high activity against s. pneumoniae 7785 with the mic value of 0.125 μg/ml. clinafloxacin showed potent broad-spectrum in vitro activity against gram-positive, gram-negative, and anaerobic pathogens [2]. clinafloxacin has been identified as the most active fluoroquinolone against s. pneumoniae compared to grepafloxacin, levofloxacin, ofloxacin, sparfloxacin, and trovafloxacin and is currently being evaluated as an antipneumococcal agent [3].
in vivo
Clinafloxacin is very effective for the therapy of penicillin-resistant, ciprofloxacin-susceptible pneumococcal meningitis in the rabbit model.
With the CS strain (2349)(Clinafloxacin MIC=0.12 μg/ml), at a dose of 10 mg/kg and 20 mg/kg per day Clinafloxacin achieves an initial reduction at 6 hr. Both are bactericidal at this point but presents regrowth at 24 hr, and the final reduction at 24 hr in mean log cfu/ml is 22.30 and 23.83, respectively. However, With the CR strain (4371)(Clinafloxacin MIC=0.5 μg/ml), Clinafloxacin even at 20 mg/kg per day does not decrease bacterial titers at any time point in this rabbit model of meningitis[3].
References
[1]. humphrey g h, shapiro m a, randinitis e j, et al. pharmacokinetics of clinafloxacin enantiomers in humans[j]. the journal of clinical pharmacology, 1999, 39(11): 1143-1150.
[2]. pan x s, fisher l m. dna gyrase and topoisomerase iv are dual targets of clinafloxacin action in streptococcus pneumoniae[j]. antimicrobial agents and chemotherapy, 1998, 42(11): 2810-2816.
[3]. jorgensen j h, weigel l m, swenson j m, et al. activities of clinafloxacin, gatifloxacin, gemifloxacin, and trovafloxacin against recent clinical isolates of levofloxacin-resistant streptococcus pneumoniae[j]. antimicrobial agents and chemotherapy, 2000, 44(11): 2962-2968.
