PENETRATION OF TROVAFLOXACIN INTO CEREBROSPINAL-FLUID IN HUMANS FOLLOWING INTRAVENOUS-INFUSION OF ALATROFLOXACIN

A single-dose study was conducted to determine concentrations of trova floxacin (CP-99,219) achieved in the cerebrospinal fluid (CSF) relativ e to those in the serum of healthy subjects after intravenous infusion of alatrofloxacin (CP-116,517), the alanyl-alanyl prodrug of trovaflo xacin. Twelve healthy subjects were administered single doses of alatr ofloxacin at a trovafloxacin equivalent of 300 mg as an intravenous in fusion over 1.0 h. CSF samples were taken by lumbar puncture at 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, and 24 h after the start of the infusion; each subject was sampled at only one time point. Serum samples were t aken from each subject at the lime of CSF collection, A mean concentra tion of 5.8 mu g of trovafloxacin per ml was present in serum 1.0 h af ter the start of the infusion. CSF/serum ratios ranged from 0.14 to 0. 33 in the postdistribution phase (5 to 24 h postinfusion), with a mean ratio of 0.25. The most common adverse events were dizziness, nausea, and rash and were mild or moderate in intensity. The potency of trova floxacin against susceptible organisms, coupled with its rapid penetra tion of CSF following the intravenous administration of alatrofloxacin , suggests that it may be useful in the treatment of bacterial meningi tis in humans.