Pharmacokinetics and Pharmacodynamics of the New Quinolones

Abstract

In this review, the authors describe the pharmacokinetic (PK) and pharmacodynamic (PD) characteristics of the new quinolones (levofloxacin, gatifloxacin, moxifloxacin, gemifloxacin, and garenoxacin) and discuss their implications on adequate therapy of patients with respiratory infections. The newer quinolones display excellent bioavailability and have longer serum half-lives than ciprofloxacin. In addition, they have the ability to concentrate in respiratory tract tissues and fluids at levels that exceed serum-drug concentrations. Also, the newer quinolones exhibit broad-spectrum activity against both susceptible and resistant organisms. Those favorable PK/PD properties make the new quinolones an attractive therapeutic alternative to traditional agents for common respiratory infections. Understanding the PK/PD of quinolone antibiotics can facilitate selection of optimal regimens to hasten response, prevent treatment failures, and minimize the development of resistance.

Safety Concerns Surrounding Quinolone Use in Children

“…The large volume of distribution of newer fluoroquinolones, together with low protein binding, results in extensive tissue and fluid distribution. 15 In terms of elimination, there is considerable variation among fluoroquinolones. Ofloxacin, levofloxacin, and gatifloxacin are predominantly excreted unchanged in the urine, whereas others undergo a certain level of hepatic metabolism prior to elimination.…”

Structural Development, Haematological Immunological and Pharmacological Effects of Quinolones

“…As grepafloxacin penetrates tissues well [88], its inhibition of IL-1 production could be important in clinical use in addition to its antibacterial effect. The combination of these two effects may make grepafloxacin useful for treating clinical infections where cytokines have been activated by endotoxin release in septicaemic states and where excessive inflammatory reaction has occurred.…”

Average bioequivalence of single 500 mg doses of two oral formulations of levofloxacin: a randomized, open-label, two-period crossover study in healthy adult Brazilian volunteers

“…community acquired and nosocomial pneumonia, skin and skin structure infections and urinary tract infections (Siewert, 2006). It has a broad spectrum antibacterial profile including Gram-positive as well as Gram-negative bacteria, and atypical organisms (Anderson, Perry, 2008;Croom, Goa, 2003;Noreddin, Haynes, Zhanel, 2005;Takahashi, Hayakawa, Akimoto, 2003). Levofloxacin is well tolerated, and is associated with few of the phototoxic, cardiac or hepatic adverse events seen with some other quinolones.…”

“…Levofloxacin and newer quinolones, when compared with older agents such as ciprofloxacin, achieve higher peak serum concentrations (C max ), resulting in higher C max /MIC (minimum inhibitory concentration) ratios, which result in excellent bacterial killing (Noreddin, Haynes, Zhanel, 2005).…”