Dose ranging study and constant infusion evaluation of ciprofloxacin

We evaluated the pharmacokinetics of 100- and 200-mg doses of ciprofloxacin, with the 200-mg dose administered either as a 30-min infusion or as a 100-mg loading dose followed by a 4-h constant infusion of 25 mg/h in six normal volunteers. No significant differences were seen in the dose-normalized area under the curve when the 100- and 200-mg 30-min administrations were compared. Differences that approached statistical significance were seen when data from either of these trials were compared with data from the constant-infusion arm. Serum clearances averaged 23.0 +/- 9.1 liters/h per 1.73 m2 for the 100-mg dose and 23.7 +/- 5.1 liters/h per 1.73 m2 for the 200-mg dose. Renal clearance accounted for approximately two-thirds of the serum clearance in each instance. Half-lives were slightly longer than 4 h. For the constant-infusion arm, serum clearance was 28.9 +/- 2.7 liters/h per 1.73 m2, with renal clearance accounting for 58% of serum clearance. Although no nonlinearities were apparent in the 100- to 200-mg dose range, larger doses, particularly in the multiple-dosing situation, may uncover nonlinearity in the disposition of ciprofloxacin.