Dose-ranging pharmacokinetic study of ciprofloxacin after 200-, 300-, and 400-mg intravenous doses

OBJECTIVE: To assess the pharmacokinetics and tolerance of ciprofloxacin after the administration of single intravenous doses of 200, 300, and 400 mg. DESIGN: Double-blind, three-period, randomized, crossover trial. SETTING: Private, university-affiliated, hospital-based, clinical research center. PATIENTS: Normal healthy male volunteers, 18–40 years of age. INTERVENTIONS: Subjects received 200-, 300-, and 400-mg single intravenous doses of ciprofloxacin via 30-minute infusions in random sequence. MAIN OUTCOME MEASURES: Serum ciprofloxacin concentrations were determined by HPLC after each dose and the results were used to derive pharmacokinetic parameters. Tolerance was assessed by reported and observed adverse events, urine microscopic examinations for crystals, and examination of intravenous infusion sites. RESULTS: The mean area under the time curve (AUC) values displayed linearity with respect to the administered dose. No statistical differences were observed in total body clearance, steady-state volume of distribution, or elimination half-life with respect to dose administered. The mean total body clearance, steady-state volume of distribution, or elimination half-life ranged from 36 to 41 L/h, 146 to 169 L, and 3.5 to 3.7 h for the 200-, 300-, and 400-mg doses, respectively. Adverse effects, including venous irritation (four subjects) and crystalluria (two subjects), were mild and did not require withdrawal of any subject from the study. Intravenous ciprofloxacin in doses ranging from 200 to 400 mg demonstrated linear pharmacokinetics. These single doses were well tolerated, although cases of transient venous irritation and crystalluria were observed.