Multiple-dose ciprofloxacin dose ranging and kinetics

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Abstract
Multiple does of i.v. ciprofloxacin over 10 min every 12 h for 1 wk to 9 healthy subjects, while 3 other subjects received placebo. Ciprofloxacin doses of 25, 50 and 75 mg were evaluated with a 1-wk washout between each dose level. Mean (.+-. SD) terminal excretion t1/2 [half-time] were 3.56 .+-. 0.66, 4.15 .+-. 0.68, and 3.46 .+-. 0.42 h for the 25, 50 and 75 mg doses. Serum clearances were 35.4 .+-. 6.8, 31.8 .+-. 3.0 and 31.3 .+-. 5.4 l/h/1.73 m2 for these doses. Urine concentrations remained above the minimal inhibitory concentration of most urinary tract pathogens for the full 12-h dosing interval at each dose. Renal clearance accounted for 65%-70% of the serum clearance, but because biologically active renally excreted metabolites were identified, values exceed the true values. The doses of ciprofloxacin i.v. injected were well tolerated and appeared adequate for treatment of urinary tract infections. For serious hospital-acquired sepsis, however, larger doses should be evaluated.