The comparative pharmacokinetics and tissue penetration of single-dose ciprofloxacin 400 mg i.v. and 750 mg po

Abstract

The pharmacokinetics of ciprofloxacin following single doses of 400 mg i.v. and 750 mg po were compared in six healthy volunteers. Concentrations of ciprofloxacin were measured in plasma, cantharides induced blister fluid and urine, by microbiological assay and high performance liquid chromatography (HPLC). Mean peak plasma concentration was 6.7 +/- 1.4 mg/L after i.v. and 3.9 +/- 1.7 mg/L after oral administration with mean elimination half-lives of 4.2 and 4.0 h respectively. Mean area under the concentration versus time curve (AUC) was greater following oral administration (19.2 +/- 1.1 mg/L.h versus 14.2 +/- 1.1 mg/L.h). Blister fluid peak concentrations following i.v. and oral administration were 2.6 +/- 1.3 mg/L and 2.28 +/- 1.2 mg/L respectively. The elimination half-life from blister fluid was 4.1 +/- 1.1 h and the AUC 13.8 +/- 1.1 mg/L.h following i.v. administration compared with 4.6 +/- 1.5 h and 20.3 +/- 1.3 mg/L.h for the oral dose. A mean of 50.8% of i.v. administered drug and 39.6% or orally administered drug was excreted in urine in 24 h as measured by HPLC. The corresponding values by microbiological assay were greater, suggesting excretion of active metabolites. Both i.v. and oral doses produced levels in blister fluid concentration above the MICs for most Enterobacteriaceae, Pseudomonas aeruginosa, Haemophilus influenzae and Neisseria spp. at 12 h post dose. The pharmacokinetic data from inflammatory fluid indicate that ciprofloxacin 400 mg i.v. is more equivalent to 750 mg po than the plasma pharmacokinetic data suggest.