Multiple-dose pharmacokinetics of ofloxacin in serum, saliva, and skin blister fluid of healthy volunteers

Abstract

The pharmacokinetics of ofloxacin were determined in six healthy volunteers after oral administration of 200 mg twice daily for 3.5 days. To study the pharmacokinetic behavior at the target site in bacterial infection of the skin, drug concentrations were determined in suction blister fluid (SBF) and cantharides blister fluid (CBF), as well as in serum and saliva. Ofloxacin was measured by a high-performance liquid chromatographic assay. Ofloxacin concentrations in saliva amounted to 61 +/- 3% of levels in serum. After the final dose, ofloxacin concentrations in blister fluid and serum declined in parallel. Terminal half-lives of ofloxacin in blister fluids (SBF, 7.0 h; CBF, 6.3 h) were in accordance with serum half-life (6.6 h). Favorable penetration into the skin is suggested by high area under the concentration-time curve ratios for blister fluid and serum (CBF, 1.1; SBF, 1.3). During repeated ofloxacin intake, drug levels in SBF and CBF at 12 h amounted to 0.94 and 1.10 micrograms/ml. Thus, ofloxacin levels in the skin are well above the MIC for 90% of strains tested for, e.g., Staphylococcus aureus, Staphylococcus epidermidis, Neisseria gonorrhoeae, and various members of the family Enterobacteriaceae. This should also hold true with respect to other tissues.