Tissue penetration of ciprofloxacin after single and multiple doses.

The pharmacokinetics and the suction-induced blister fluid penetration of ciprofloxacin were compared after a single dose (500 mg) and after multiple dosing (500 mg q8h for 13 doses). Significantly higher peak levels of ciprofloxacin in serum were observed after multiple dosing (3.51 versus 2.26 micrograms/ml; P less than 0.01). Increased elimination half-life occurred after multiple dosing; this seems to be mostly related to decreased systemic clearance secondary to a diminished nonrenal clearance (240.0 versus 125.0 ml/min). Ciprofloxacin appeared rapidly in the blister fluid, and the percentage of penetration (AUC0-tBF/AUC0-t serum) yielded values of 88.8 versus 84.7% after single and multiple doses, respectively. Ciprofloxacin levels in serum and blister fluid at the end of the dosing interval (8 h) were superior or almost superior to MICs for sensitive organisms including Pseudomonas aeruginosa. Comparative studies of ciprofloxacin metabolite excretion after multiple doses in healthy subjects and in renal insufficiency patients are needed.