The pharmacokinetics and tissue penetration of the fluoroquinolones

Abstract

There are marked differences among the pharmacokinetic properties of the quinolones. Absorption of norfloxacin, ciprofloxacin, and enoxacin is incomplete, whereas the bioavailability of pefloxacin, ofloxacin and fleroxacin is almost 100%. With the exception of norfloxacin the quinolones can be taken orally or administered by the parenteral route. Maximum serum concentrations vary between 1.5 and 10.7 micrograms/ml depending on the dose and antibiotic given. Respective AUC's of 78 and 5.5 micrograms/ml-h are observed following the administration of 400 mg of either fleroxacin or norfloxacin. Protein binding is low (less than or equal to 30%) and apparent volume of distribution is between 1.5 and 3.1 liters/kg. Pefloxacin undergoes extensive metabolism in the liver (85%) while less than 5% of ofloxacin is transformed. Norfloxacin and ciprofloxacin have the shortest half-lives (+/- 4h), while fleroxacin and pefloxacin have the longest (10-12h). In renal failure, no adjustments are necessary with pefloxacin, while major modifications in dosing interval and/or doses are needed when ofloxacin is given. The pharmacokinetics of the quinolones is disturbed in elderly subjects and cystic fibrosis patients. Concurrent administration of antacids which contain aluminum hydroxide or magnesium hydroxide leads to reduced absorption, while probenecid blocks the tubular secretion of some quinolones. These drugs diffuse rapidly in extravascular fluid, saliva, urine, kidney, prostate, bile and peritoneal fluid. Slightly lower levels can be detected in fibrin clots, cerebrospinal fluid and the heart. Ciprofloxacin offers the best therapeutic ratio (concentration serum-tissue/minimum inhibitory concentration) against Pseudomonas aeruginosa.