Hepatobiliary elimination of trovafloxacin and metabolites following single oral doses in healthy volunteers.
Trovafloxacin, a fluoronaphthyridone derivative related to fluoroquinolones, has significant activity against gram-negative and gram-positive pathogens, including penicillin-resistant Streptococcus pneumoniae, anaerobes and atypical organisms, good tissue penetration and a long elimination half-life. Following oral administration, less than 10% of the dose is renally eliminated as unchanged drug. Hepatobiliary elimination of trovafloxacin was examined by comparing the time course and bile and serum concentrations of trovafloxacin and its metabolites following oral administration to three patients with in-dwelling nasobiliary catheters or T-tubes. Following a single 200 mg oral dose, the mean maximum plasma trovafloxacin concentration was 2.0+/-0.4 mg/l, the area under the concentration-time curve 22.0+/-5.5 mg x h/l and the elimination half-life 8.5 h. Values in bile for the same subjects were 27.8+/-9.6 mg/l, 327.7+/-142.9 mg x h/l and 10.7 h. Corresponding values for the N-acetyl metabolite in bile were 3.8+/-3.4 mg/l, 35.3+/-29.8 mg x h/l and 8.3 h. The mean bile : serum ratio of trovafloxacin was 14:9 and consistent with biliary elimination. Serum concentrations of trovafloxacin in this study were similar to those reported in healthy volunteers. Bile concentrations of trovafloxacin substantially exceeded those of the N-acetyl metabolite, suggesting efficient clearance of the metabolite or that hepatic metabolism of trovafloxacin is not extensive.
Department of Pharmacology, The University of Texas Health Science Center at San Antonio, South Texas Veterans Health Care System, 78284, USA.
G
G
Melnik
W H
WH
Schwesinger
R
R
Teng
L C
LC
Dogolo
J
J
Vincent
D000284:Administration, Oral; D000328:Adult; D000890:Anti-Infective Agents / Q000008:administration & dosage / Q000097:blood / Q000378:metabolism* / Q000493:pharmacokinetics*; D019540:Area Under Curve; D001646:Bile / Q000378:metabolism*; D005260:Female; D024841:Fluoroquinolones; D006207:Half-Life; D006801:Humans; D008099:Liver / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009287:Naphthyridines / Q000008:administration & dosage / Q000097:blood / Q000378:metabolism* / Q000493:pharmacokinetics*
D000890:Anti-Infective Agents; D024841:Fluoroquinolones; D009287:Naphthyridines; C080163:trovafloxacin