• Quinolones

  • Fluoroquinolones Pharmacokinetics

    • Absorption

      Absorption Audio Overview

      • Oral absorption of quinolones is considered moderate to excellent and are generally well absorbed from the gastrointestinal tract.

        • There is some variability between different agents.¹ 

        • For example, the oral bioavailability of levofloxacin is about 99%.

          • By contrast the oral bioavailability of ciprofloxacin is 70%, delafloxacin 59% and moxifloxacin 89%.¹

          • Given the good oral bioavailability of these agents, oral doses of fluoroquinolones may be substituted for intravenous administration with only slight changes in doses (for oral ciprofloxacin and delafloxacin as examples).¹

        • However, the presence of multivalent cations complexed with the fluorquinolone can substantially reduce bioavailability.

          • This reduction is reflected in reduced area-under-the-curve (AUC)  and C_max values.

          • For example, with ciprofloxacin the reduction in these pharmacokinetic parameters is most pronounced with coadministration of sucralfate, magnesium, or aluminum.¹

    • Distribution

      Distribution Audio Overview

      • Fluoroquinolones exhibit large volume of distribution with the agent penetrating widely into body of fluids and tissues.

        • The volume of distribution may be of the order of 1.5 L/kg, although the volume of distribution for ciprofloxacin tends to be on the higher end at (2-3 L/kg).⁴

        • Serum concentrations are typically higher than serum concentrations and, for ciprofloxacin, therapeutic concentrations are achieved and saliva, lymph, bronchial secretions, bile, prostatic tissue and urine.⁴

        • CSF concentration of ciprofloxacin tends to increase during active meningeal inflammation.⁵

        • Fluoroquinolones accumulate in phagocytes which may prove useful in targeting intracellular bacteria.⁸

          • Fluoroquinolones concentrates in macrophages⁸ showing activity against of variety of intracellular bacteria including Listeria monocytogenes and Staphylococcus aureus.⁶

            • Not all quinolones are equally concentrated intracellularly with ciprofloxacin < levofloxacin < garenoxacin < moxifloxacin.⁶

        • Quinolones bind to plasma protein to a limited extent.⁷

        • Fluoroquinolones have been found in human breast milk, suggesting the possibility of exposure of nursing infants.⁸

    • Metabolism

      Metabolism Audio Overview

      • Ciprofloxacin is metabolized to limited extent by the liver.

        • Four active metabolite of ciprofloxacin result: sulfo-ciprofloxacin, oxo-ciprofloxacin, N-acetylciprofloxacin and desethyleneciprofloxacin.^11,12 

        • Ciprofloxacin itself is an inhibitor of cytochrome P450 1A2 (CYP1A2).

          • Therefore administration of ciprofloxacin with other drugs that are metabolized by CYP1A2 may increase the plasma levels of these agents, potentially to toxic levels.⁴

      • Levofloxacin undergoes very limited hepatic metabolism, being mainly excreted in the urine.¹⁰

      • Moxifloxacin:  About 52% of an oral or IV dose of moxifloxacin is metabolized by the liver, mainly by glucuronide (14%)and sulfate conjugation (38%) (phase II reactions). which results in inactive metabolites.¹³

        • Moxifloxacin metabolism is only slightly influenced by cytochrome P450 enzymes.⁹

    • Excretion

      Excretion Audio Overview

      • Most quinolones are cleared mainly by the kidney, requiring dose adjustment in the case of reduced renal function.⁸

        • Ciprofloxacin and levofloxacin are examples of quinolones eliminated by the kidneys.

          • For levofloxacin, about 87% of dose is excreted unchanged in the urine within about two days and an additional smaller percentage (about 4%) in the feces.¹⁴

          • For ciprofloxacin, about 30% following oral administration is found unchanged in the urine; whereas, about 46% of an IV dose may be recovered unmetabolized in urine.¹⁵

        • Moxifloxacin differs in that most of the drug is cleared non-renally with only about 20% of the dose excreted in the urine unchanged.

          • An additional 25% is excreted unchanged in feces with the remaining percentage accounted for as metabolites.¹⁶

          • About 50% of moxifloxacin elimination is hepatic (glucuronide and sulfate conjugation)¹³

      • For certain quinolones, including ciprofloxacin, renal clearance exceeds glomerular filtration rate, suggesting net tubular secretion.

        • Consequently, at least ciprofloxacin and possibly other quinolones utilize active transport in excretion in addition to filtration.¹⁸

July, 2025