The comparative pharmacokinetics and tissue penetration of single-dose ciprofloxacin 400 mg iv 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.

Evolution of Ciprofloxacin-Resistant Staphylococcus aureus in In Vitro Pharmacokinetic Environments

“…These simulations were designed to achieve total drug concentrations in the central and peripheral compartments that mimicked profiles observed in the serum and skin blister fluid of healthy adults over time (10,32,52). Three experimental dosage simulations were also examined.…”

“…Drug, diluent, and elimination pumps of the in vitro system were set at appropriate rates to simulate a ciprofloxacin elimination half-life of 4 h based on pharmacokinetics in adults with normal renal function (10,51,52). Growth control experiments for each strain were conducted over 36 h at the same pump rates used for ciprofloxacin dosage regimen simulations.…”

Pharmacokinetics and Pharmacodynamics of Levofloxacin againstStreptococcus pneumoniaeandStaphylococcus aureusin Human Skin Blister Fluid

“…Fourteen hours later, the plasters were removed. SBF was sampled by puncture of the blisters with a 22-gauge needle for ex vivo determination of the phagocytic-bactericidal activity against the test strain before (0 h) and at seven time points following (1,2,3,5,7,9, and 24 h) drug administration, as previously described (25). The pharmacokinetic parameters were calculated from the serum and SBF samples of all 20 volunteers.…”

Comparative pharmacokinetics of Aspegic 1000 mg i.v. versus 1000 mg i.m. thrice daily

“…routes of administration in order to obtain information as to the conditions necessary to establish them as potent alternative ways of treatment. Various experimental studies have been performed for this purpose (15,16). A numerical model taking all the known facts into account was established and used.…”

“…Aspegic was selected as the drug for at least three reasons: (i) it has often been used as a drug model (17); (ii) good data can be found in the literature (18,19), while varying results have been obtained for other drugs, such as ciprofloxacin (15,16); and (iii) Aspegic is also a very effective drug, and for various therapies it must be administered over a long period of time (5-8).…”