A new trifluorinated quinolone: Ro 23-6240 (AM 833)

Ro 23-6240 is a new fluoroquinolone displaying pronounced activity against a wide range of Gram-positive and Gram-negative pathogens. In order to obtain information about the absorption, distribution and excretion of this quinolone in man, six healthy volunteers received in cross-over an intravenous infusion of 100 mg Ro 23-6240 and an oral dose of two tablets corresponding to 400 mg Ro 23-6240. Serial plasma and urine samples were assayed for unchanged substance by HPLC with subsequent fluorescence or UV detection. Pharmacokinetics were evaluated from these data assuming a two-compartment open model. Characteristic of this new antibacterial are the high plasma levels following oral administration (Cmax: 4.5 micrograms/ml) and the long elimination half-lives (8-12 h). Both these parameters are favourable kinetic prerequisites for a once-a-day dosage regimen. In addition, the volume of distribution at steady state clearly exceeds 1 l/kg and points to good tissue penetration. Total systemic clearance was 122 ml/min and total renal clearance reached 89 ml/min. Within 96 h, 60-70% of the administered dose was recovered from urine as unchanged drug. The absolute bioavailability (extent of absorption) of the tablet amounted to 96%, indicating a complete absorption of this galenic formulation.