Comparative pharmacokinetic parameters of new systemic fluoroquinolones.
The recent piperazinyl-substituted mono-fluoroquinolones represent a family with some common features on the one hand, and some variable parameters on the other. Some of the common features are: same mechanism of action (DNA-gyrase inhibitors of the A subunit of topoisomerase); pH-dependent antibacterial activity; a rather long post-antibiotic effect for both Gram-positive and Gram-negative bacteria; same physicochemical properties (organic acids, high pKa, lipophilicity). Common pharmacokinetic parameters include low protein binding (less than 50%); high volume of distribution (greater than 1 l/kg) with good tissue concentrations attainable in lymph, blister fluid, renal tissue prostate, bronchial secretions, saliva, aqueous humour, CSF, bone and bile; good intracellular penetration in macrophages and polynuclear neutrophils; high peak urinary concentrations, markedly exceeding the MIC for virtually all bacterial urinary tract pathogens, even accounting for the increase in MIC in the urine, especially at lower (acidic) pH; low extraction ratio dialysis; similar adverse reactions (CNS, gastrointestinal, photosensitivity, tendo-articular and cartilage toxicity). However, most other pharmacokinetic parameters are different from one fluoroquinolone to the other: oral bioavailability, peak serum levels (Cmax) as a measure of bioavailability, terminal half-life of elimination (t1/2) are all variable. The extent of metabolic biotransformation varies greatly, the two extremes being ofloxacin, showing a high metabolic stability and pefloxacin, highly metabolized. The degree of antibacterial activity of different metabolites also varies widely.(ABSTRACT TRUNCATED AT 250 WORDS)
Neuman
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D000900:Anti-Bacterial Agents / Q000378:metabolism* / Q000494:pharmacology; D001419:Bacteria / Q000187:drug effects; D001646:Bile / Q000032:analysis; D001711:Biotransformation; D006801:Humans; D007668:Kidney / Q000378:metabolism; D007700:Kinetics; D011804:Quinolines / Q000378:metabolism* / Q000494:pharmacology
D000900:Anti-Bacterial Agents; D011804:Quinolines