Fluoroquinolone pharmacokinetics

Antimicrobial action peculiarities and pharmacokinetics of novel fluoroquinolones 98MI6. 

Comparative pharmacokinetics of lomefloxacin and other fluoroquinolones 98MI8. 

Pharmacokinetic interaction between fluoroquinolones and other drugs 98MI5. 

Integration of both pharmacokinetic and pharmacodynamic properties of an agent is important when choosing antimicrobial therapy to ensure efficacy and prevent resistance. Antibiotics may demonstrate concentration-dependent (aminoglycosides and fluoroquinolones) or time-depen-dent (/l-1 acta ms) bactericidal effects. 

Because of its pharmacokinetic features (pronounced bioaccessability upon oral use, diffusion to tissues and permeation into them, broad spectrum of antibacterial activity, and so on), fluoroquinolones have considerable potential for treating infections of practically any anatomic localization. Fluoroquinolones are very effective in treating infections of the respiratory tract, urinary tract, bones, skin, soft tissues, and so on. 

In terms of pharmacokinetics, LVX has an excellent profile. With an oral dose of 500 mg, LVX has a bioavailability of >99%, an AUC range of 41.9-47.7 mgh/mL, Cmax of 4.5-6.2 mg/mL, a clearance of 10.5-11.9 L/h, and a volume of distribution (Vd) of 1.3 L/kg (Hurst et al., 2002). In terms of protein bound material, only 24-38% is affected (Fish, 2003). Like other fluoroquinolones, there is a 19-44% AUC reduction when co-administered with an aluminum or magnesium antacid or iron sulfate (Qaqish and Polk, 2003). The major metabolite of levofloxacin arises from glucuronidation (Brysk-ier, 2005). 

Mecfianism of Action A fluoroquinolone that inhibits two enzymes, topoisomerase II and IV, in susceptible microorganisms. Therapeutic Effect Interferes with bacterial DNA replication. Prevents or delays resistance emergence. Bactericidal. Pharmacokinetics Well absorbed from the GI tract after PO administration. Protein binding 20%. Widely distributed. Metabolized in liver. Primarily excreted in urine. Half-life 7-14 hr. 

Merino G, Alvarez Al, Pulido MM, et al. Breast cancer resistance protein (BCRP/ ABCG2) transports fluoroquinolone antibiotics and affects their oral availability, pharmacokinetics, and milk secretion. Drug Metab Dispos 2006 34 690-695. 

A comparative study of the pharmacokinetic and pharmacodynamic properties of the more modern fluoroquinolones [218,219], as well as overviews on the pharmacokinetics [163,220] and pharmacodynamics [221] of moxifloxacin, can be found in the literature. 

Moxifloxacin s pharmacokinetics are neither age- nor sex-dependent [228], although special measures may be required when treating older patients with restricted organ function with fluoroquinolones [229]. 

Aminimanizani A, Beringer P, Jelliffe R. Comparative pharmacokinetics and pharmacodynamics of the newer fluoroquinolone antibacterials. Clin. Pharma-cohinet., 2001, 40, 169-187,... 

The pharmacokinetic properties of fluoroquinolone antibacterial agents have been well described [23]. Gemifloxacin is rapidly absorbed with a time to maximum plasma concentration (T ax) of 0.5-2 h in healthy subjects and displays linear pharmacokinetics over the dose range studied (20-800 mg), with an apparent plasma terminal half-life (fi/2) after single or repeated administration of about 8 h. A minimum of 20-30% of the oral dose is excreted imchanged in the urine. Following repeat oral... 

Co-administration of fenbufen and fluoroquinolones has been associated with seizures (141). The structure at the 7-position greatly affects the risk of NSAID-potentiated nervous system effects. Fluoroquinolones with unsubstituted piperazinyl rings (ciprofloxacin, enox-acin, and norfloxacin) have a strong interaction with NSAIDs (142). The increased risk of seizures is not caused by increased serum concentrations of fluoroquinolones, since their pharmacokinetics are not altered by NSAIDs (143). The mechanism has been suggested to be facilitation by fenbufen of the fluoroquinolone-induced inhibition of GABAa receptor function in the hippocampus and frontal cortex (144). 

Sambatakou H, Giamarellos-Bourboulis EJ, Galanakis N, Giamarellou H. Pharmacokinetics of fluoroquinolones in uncompensated cirrhosis the significance of penetration in the ascitic fluid. Int J Antimicrob Agents 2001 18(5) 441-4. 

---