title: Pharmacokinetics of intravenous trovafloxacin in critically ill adults.
abstract: The pharmacokinetic disposition of numerous antimicrobial agents is altered in critically ill patients. Pharmacokinetics of trovafloxacin, a fluoroquinolone indicated specifically for severe, life-threatening infections in the intensive care unit, have not been well studied in this population. We characterized the pharmacokinetic disposition of trovafloxacin after administration of alatrofloxacin, the intravenous prodrug, in critically ill adults. Seven patients (3 men, 4 women; mean +/- SD age 59.4 +/- 20.6 yrs; baseline aspartate aminotransferase [AST]/alanine aminotransferase [ALT] 66.0 +/- 40.6/51.5 +/-37.5 IU/L; median Acute Physiology and Chronic Health Evaluation [APACHE II] score 27, range 15-32) were studied at estimated steady state. Calculated (mean +/- SD) half-life, clearance at steady state, and volume of distribution in all patients were 10.9 +/- 1.8 hours, 161.3 +/- 41.1 ml/minute, and 1.4 +/- 0.4 L/kg. In patients receiving 300 mg, maximum concentration, minimum concentration, and area under the curve from 0-24 hours were 3.6 +/- 0.5 mg/L, 0.6 +/- 0.3 mg/L, and 34.2 +/- 10.6 mg x hr/L, respectively. These results are consistent with published values in other patient populations, indicating that trovafloxacin pharmacokinetics are not substantially altered in critically ill patients with normal or mildly impaired hepatic function.
authors.affiliation: Department of Pharmacy Practice, College of Pharmacy, University of Nebraska Medical Center, Omaha 68198-6045, USA.
authors.forename: K M
authors.initials: KM
authors.lastname: Olsen
authors.forename: J A
authors.initials: JA
authors.lastname: Rebuck
authors.forename: T
authors.initials: T
authors.lastname: Weidenbach
authors.forename: D N
authors.initials: DN
authors.lastname: Fish
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000410:Alanine Transaminase / Q000097:blood; D000890:Anti-Infective Agents / Q000097:blood / Q000493:pharmacokinetics*; D019540:Area Under Curve; D001219:Aspartate Aminotransferases / Q000097:blood; D016638:Critical Illness / Q000628:therapy*; D005260:Female; D024841:Fluoroquinolones; D006207:Half-Life; D006801:Humans; D007275:Injections, Intravenous; D007362:Intensive Care Units; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D009287:Naphthyridines / Q000097:blood / Q000493:pharmacokinetics*; D011355:Prodrugs / Q000493:pharmacokinetics*; D011446:Prospective Studies
chemical_list: D000890:Anti-Infective Agents; D024841:Fluoroquinolones; D009287:Naphthyridines; D011355:Prodrugs; C080163:trovafloxacin; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase