Single- and multiple-dose administration, dosing regimens, and pharmacokinetics of trovafloxacin and alatrofloxacin in humans.
A simplified dosing algorithm for trovafloxacin was evaluated following a single-dose infusion of alatrofloxacin at trovafloxacin equivalent doses of 30, 100, 200, 300 and 400 mg (57 subjects), and multiple doses of 200, 300 and 400 mg (30 subjects). Maximum serum concentration and area under the concentration-time curve for trovafloxacin increased with dose. Trovafloxacin clearance (82-85 ml x h/kg) and volume of distribution (1.3-1.6 l/kg) were independent of dose. Infusion of alatrofloxacin at a trovafloxacin equivalent dose of 300 mg at 1, 2 or 3 mg/ml over 1 h did not alter the pharmacokinetics of trovafloxacin. A plot of the weight-adjusted dose of trovafloxacin in individual subjects against the maximum serum concentration following single and multiple dosing, indicated that the maximum serum concentration increased 1 microg/ml for each 1 mg/kg of trovafloxacin administered. Thus, a prior knowledge of the desired serum concentration will permit appropriate dosing without the use of complex nomograms in patients with normal hepatic function.
Central Research Division, Pfizer Inc, Groton, CT 06340, USA.
J
J
Vincent
L
L
Dogolo
B A
BA
Baris
S A
SA
Willavize
R
R
Teng
D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000890:Anti-Infective Agents / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*; D004334:Drug Administration Schedule; D024841:Fluoroquinolones; D006207:Half-Life; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D009287:Naphthyridines / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*; D011355:Prodrugs / Q000008:administration & dosage* / Q000493:pharmacokinetics*
D000890:Anti-Infective Agents; D024841:Fluoroquinolones; D009287:Naphthyridines; D011355:Prodrugs; C106856:alatrofloxacin; C080163:trovafloxacin