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Pharmacokinetics of Ofloxacin Enantiomers after Intravenous Administration for Antibiotic Prophylaxis in Biliary Surgery
Author(s) -
Gascón A. R.,
Campo E.,
Hernández R. M.,
Calvo B.,
Errasti J.,
Muñoz J. L. Pedraz
Publication year - 2000
Publication title -
the journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.92
H-Index - 116
eISSN - 1552-4604
pISSN - 0091-2700
DOI - 10.1177/00912700022009602
Subject(s) - ofloxacin , pharmacokinetics , levofloxacin , pharmacology , enantiomer , antibacterial agent , ciprofloxacin , medicine , chemistry , antibiotics , urology , biochemistry , organic chemistry
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 1 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 (≥ 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, AUC0‐ 0‐∞ (22.30 ± 2.72 mgh/L for S‐(−)‐ofloxacin vs. 20.50 ± 2.06 mgh/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.