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 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·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.