Pharmacokinetics of ofloxacin enantiomers after intravenous administration for antibiotic prophylaxis in biliary surgery

The pharmacokinetics of S-(-)- and R-(+)-ofloxacin, enantiomers of the fluoroquinolone ofloxacin, were characterized after prophylactic administration in 15 patients undergoing elective biliary surgery. A single dose of ofloxacin 400 mg given intravenously as an infusion was administered I hour before surgery. Plasma levels of S-(-)- and R-(+)-ofloxacin showed very small differences between both enantiomers, although the ratio of S-(-)- to R-(+)-enantiomer concentration in plasma showed significant differences (p < 0.05) at 4 and 12 hours. Adequate S-(-)-ofloxacin (levofloxacin, the active enantiomer) plasma levels (greater than or equal to minimum inhibitory concentration [MIC90] for Escherichia coli) were found throughout the procedure. For pharmacokinetic parameters, the authors found small but statistically significant differences (p < 0.05) in the area under the concentration-time curve, AUC(0-infinity)(22.30 +/- 2.72 mg h/L for S-(-)-ofloxacin vs. 20.50 +/- 2.06 mg h/L for R-(+)-ofloxacin), and in the clearance (0.15 +/- 0.04 L/h/Kg for S-(-)-ofloxacin vs. 0.16 + 0.04 L/h/Kg for R-(+)-ofloxacin). To test the penetration of ofloxacin enantiomers into tissues, the authors measured levels in subcutaneous cell tissue and gallbladder cell tissue. They did not observe statistical differences between the two isomers, which means that distribution is not an estereoselective process. Enantiomer levels in these two tissues decreased rapidly, but the highest concentrations were reached during the 4 first hours (i.e., when the surgical procedure was being performed). In conclusion, with the prophylactic treatment used, levofloxacin plasma and tissue levels are high enough to prevent surgical infections. (C) 2000 the American College of Clinical Pharmacology.