Fluoroquinolones distribution volumes

Fluoroquinolones distribute into most tissues with an apparent volume of distribution of 1.5 to 2L/kg. They have serum half-lives of 4 hours and renal clearance of 6mL/rain/kg clearance is reduced in renal failure. They are -40% protein bound and metabolized by hepatic conjugation (UGT) they undergo little phase I metabolism. Symptoms of toxicity include restlessness, diarrhea, and gastrointestinal upset. Skin rash may be a sign of sensitivity to fluoroquinolones. 

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). 

ABSORPTION, FATE, AND EXCRETION The quinolones are weU absorbed after oral administration and are widely distributed. Peak serum levels of the fluoroquinolones occur within 1-3 hours of an oral dose of 400 mg. Relatively low serum levels are reached with norfloxacin and limit its usefulness to the treatment of urinary tract infections. Food does not impair oral absorption but may delay the time to peak serum concentrations. Oral doses in adults are 200-400 mg every 12 hours for ofloxacin, 400 mg every 12 hours for norfloxacin and pefloxacin, and 250-750 mg every 12 hours for ciprofloxacin. Bioavailabrlity of the fluoroquinolones exceeds 50% for all agents and 95% for several. The serum half-lives range from 3 to 5 hours for norfloxacin and ciprofloxacin to 20 hours for sparfloxacin. The volume of distribution of quinolones is high, with concentrations in urine, kidney, lung and prostate tissue, stool, bUe, and macrophages and neutrophils higher than serum levels. Quinolone concentrations in CSF, bone, and prostatic fluid are lower than in serum. Pefloxacin and ofloxacin levels in ascites fluid approach serum levels, and ciprofloxacin, ofloxacin, and pefloxacin have been detected in human breast milk. 

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