Pharmacokinetics and penetration into inflammatory fluid of trovafloxacin (CP-99,219)

Abstract

A single 200-mg oral dose of trovafloxacin (CP-99,219) was given to each of eight healthy male volunteers, and the concentrations of the drug were measured in plasma, cantharides-induced inflammatory fluid, and urine over the subsequent 36 h. The mean maximum concentration observed in plasma was 2.9 micrograms/ml at a mean time of 0.75 h postdose. The mean maximum concentration observed in inflammatory fluid was 1.2 micrograms/ml at 4.0 h postdose. The mean elimination half-life in plasma was 7.8 h. The overall penetration into inflammatory fluid was 64%, as assessed by determining the ratio of the area under the concentration-time curves. Recovery of the dose in urine within the first 36 h postdose was 5.0% of the administered dose. Our results indicate that trovafloxacin, at a dosage of 200 mg once or twice daily, should be adequate for the treatment of systemic infections caused by most common bacterial pathogens.

Trovafloxacin: An Overview

“…The pharmacokinetics of alatrofloxacin and trovafloxacin are summarized in Table 4. 30,31,34,35 Absorption A randomized, two-way, crossover study determined the bioavailability of trovafloxacin in 12 fasting, healthy volunteers. 34 Subjects were given either two 100-mg tablets of trovafloxacin or the equivalent dose of intravenous alatrofloxacin.…”

“…The pharmacokinetics and penetration into inflammatory fluid of a single oral dose of trovafloxacin 200 mg were studied in eight healthy male volunteers (mean age 26 yrs, range 18-43 yrs; mean weight 73.1 kg, range 60.0-87.0 kg). 35 Trovafloxacin concentrations in serum, urine, and cantharide-induced inflammatory fluid and plasma concentrations were fitted to a two-compartment model with first-order elimination from the central compartment. Blister fluid concentrations were fitted to a onecompartment model with first-order input.…”

Pharmacokinetics and Inflammatory-Fluid Penetration of Moxifloxacin following Oral or Intravenous Administration

“…Preliminary information suggests that moxifloxacin has an elimination half-life (t 1/2 ) appropriate to once-daily dosing (5,6). In this crossover study, the pharmacokinetics and penetration of moxifloxacin into an inflammatory exudate (7) were examined following a single 400-mg dose given by the oral or intravenous (i.v.) route.…”

Trovafloxacin: A New Fluoroquinolone

“…13 In a multiple-dose pharmacokinetic study, 14 steady-state serum concentrations were reached by the third daily dose. The mean C max following 100-and 300-mg once daily doses were 1.1 and 3.3 µg/mL, respec-…”

“…The mean C max in inflammatory fluid was 2.9 µg/mL, reached at a mean time of 0.75 hours. 13 Trovafloxacin has good penetration into prostatic tissue. Following a dosing schedule of trovafloxacin 200 mg once daily for 3 days, the mean prostatic tissue concentrations were 1.5, 1.2, and 0.4 µg/g at 2-6, 6 -12, and 12-30 hours, respectively.…”