caa a22 4500 397591098 CHVBK 20180308164938.0 cr unu---uuuuu 161202e199605 xx s 000 0 eng 10.1093/jac/37.5.955 doi (NATIONALLICENCE)oxford-10.1093/jac/37.5.955 Multiple-dose pharmacokinetics and safety of trovafloxacin in healthy volunteers [Elektronische Daten] [Renli Teng, Theodore E. Liston, Stephen C. Harris] The multiple-dose pharmacokinetics and safety of trovafloxacin (CP-99,219), a new fluoroquinolone antibacterial agent, were evaluated in healthy male volunteers. Trovafloxacin was administered orally at 100 or 300 mg as a single dose followed by a 3 day washout period, and then was dosed once-daily for 14 consecutive days. Multiple serum and urine samples were collected on days 1 and 17 and were analysed for trovafloxacin concentrations by HPLC-UV. Following single doses, the mean Cmax values (mean±s.D.) were 1.0±0.3 and 2.9±0.4 mg/L for the 100 and 300 mg, respectively; those after 14-day consecutive daily dosing (day 17) were 1.1±0.2 and 3.3±0.5 mg/L, respectively. Trovafloxacin was rapidly absorbed and reached Cmax approximately 1 h after dosing. The mean values of T1/2 associated with the 100 and 300 mg doses were 9.2± 1.2 on day 1 and 10.5±0.7 h on day 17; those after the 300 mg doses were 10.5±1.4 and 12.2±1.9 h, respectively. The cumulative urinary recovery of unchanged drug averaged 5.3% of the administered dose. Trovafloxacin renal clearance was 0.43±0.09 L/h. The free fraction of the drug in plasma was 23.8± 6.1 %. The renal clearance, half-life and unbound fraction did not change over the course of 2 weeks of multiple dosing. Steady-state serum concentrations were attained by the third daily dose, with approximately 1.3-fold accumulation. Both doses of trovafloxacin were well tolerated, and no significant changes in any laboratory safety parameters were detected. This study shows that the pharmacokinetics of trovafloxacin are linear and stationary and that steady-state serum concentrations above the MICs for most susceptible pathogens attained. © 1996 The British Society for Antimicrobial Chemotherapy Original articles nationallicence Teng Renli Central Research Division, Pfizer Inc., Groton, CT 06340, USA aut Liston Theodore E. Central Research Division, Pfizer Inc., Groton, CT 06340, USA aut Harris Stephen C. Central Research Division, Pfizer Inc., Groton, CT 06340, USA aut Journal of Antimicrobial Chemotherapy Oxford University Press 37/5(1996-05), 955-963 0305-7453 37:5<955 1996 37 jac https://doi.org/10.1093/jac/37.5.955 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1093/jac/37.5.955 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Teng Renli Central Research Division, Pfizer Inc., Groton, CT 06340, USA aut NATIONALLICENCE 700 1- Liston Theodore E. Central Research Division, Pfizer Inc., Groton, CT 06340, USA aut NATIONALLICENCE 700 1- Harris Stephen C. Central Research Division, Pfizer Inc., Groton, CT 06340, USA aut NATIONALLICENCE 773 0- Journal of Antimicrobial Chemotherapy Oxford University Press 37/5(1996-05), 955-963 0305-7453 37:5<955 1996 37 jac Metadata rights reserved CC BY-NC-4.0 http://creativecommons.org/licenses/by-nc/4.0 nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-oxford