Pharmacokinetics of intravenous trovafloxacin in critically ill adults

The pharmacokinetic disposition of numerous antimicrobial agents is altered in critically ill patients. Pharmacokinetics of trovafloxacin, a fluoroqui nolone indicated specifically for severe, life-threatening infections in th e intensive care unit, have not been well studied in this population. We ch aracterized the pharmacokinetic disposition of trovafloxacin after administ ration of alatrofloxacin, the intravenous prodrug, in critically ill adults . Seven patients (3 men, 4 women; mean +/- SD age 59.4 +/- 20.6 yrs; baseli ne aspartate aminotransferase [AST]/alanine aminotransferase [ALT] 66.0 +/- 40.6/51.5 +/- 37.5 IU/L; median Acute Physiology and Chronic Health Evalua tion [APACHE II] score 27, range 15-32) were studied at estimated steady st are. Calculated (mean ft SD) half-life, clearance at steady stare, and volu me 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 conc entration, 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 . hr/l, respe ctively. These results are consistent with published values in other patien t populations, indicating that trovafloxacin pharmacokinetics are not subst antially altered in critically ill patients with normal or mildly impaired hepatic function.