Pharmacokinetics of unbound linezolid in plasma and tissue interstitium of critically ill patients after multiple dosing using microdialysis.

The antimicrobial agent linezolid is approved for the treatment of severe infections caused by, e.g., methicillin-resistant Staphylococcus strains.

The effect of food on plasma and tissue concentrations of linezolid after multiple doses.

In the present pilot study we investigated the effect of food ingestion on target site pharmacokinetics of linezolid, the first clinically approved oxazolidinone. For this purpose we determined free concentrations of linezolid at steady state in the interstitial space fluid of skeletal muscle and subcutaneous adipose tissue under fasting and non-fasting conditions in healthy volunteers (n = 9) by means of in vivo microdialysis. Ingestion of food led to a marked delay in the time to reach the peak concentration (T(max)), whereas the area under the concentration-time curve from 0 to 24 h (AUC(0-24 h)) remained unchanged.

Favourable dermal penetration of diclofenac after administration to the skin using a novel spray gel formulation.

Aims: The study was designed to evaluate the relative bioavailability of diclofenac in plasma, subcutaneous adipose and skeletal muscle tissue after repeated topical administration using MIKA Diclofenac Spray Gel (4%), a novel formulation, and after oral dosing using VOLTAREN 50 mg enteric coated tablets.

Methods: Diclofenac (48 mg) was administered topically three times daily for 3 days onto a defined area of the thigh of 12 healthy males. After a 14-day wash out period, subjects were orally treated with 50 mg diclofenac three times daily for 3 days.

Increase of microcirculatory blood flow enhances penetration of ciprofloxacin into soft tissue.

The present study addressed the effect of microcirculatory blood flow on the ability of ciprofloxacin to penetrate soft tissues. Twelve healthy male volunteers were enrolled in an analyst-blinded, clinical pharmacokinetic study. A single intravenous dose of 200 mg of ciprofloxacin was administered over a period of approximately 20 min.

Penetration of linezolid into soft tissues of healthy volunteers after single and multiple doses.

The present study tested the ability of linezolid to penetrate soft tissues in healthy volunteers. Ten healthy volunteers were subjected to linezolid drug intake at a dose of 600 mg twice a day for 3 to 5 days. The first dose was administered intravenously.

Pharmacokinetics of telithromycin in plasma and soft tissues after single-dose administration to healthy volunteers.

By use of microdialysis we assessed the concentrations of telithromycin in muscle and adipose tissue to test its ability to penetrate soft tissues. The ratios of the area under the concentration-versus-time curve from 0 to 24 h to the MIC indicated that free concentrations of telithromycin in tissue and plasma might be effective against Streptococcus pyogenes but not against staphylococci and human and animal bite pathogens.

Tissue pharmacokinetics of levofloxacin in human soft tissue infections.

Aims: The present study addressed the ability of levofloxacin to penetrate into subcutaneous adipose tissues in patients with soft tissue infection.

Methods: Tissue concentrations of levofloxacin in inflamed and healthy subcutaneous adipose tissue were measured in six patients by microdialysis after administration of a single intravenous dose of 500 mg. Levofloxacin was assayed by high-performance liquid chromatography.

Comparison of UV and tandem mass spectrometric detection for the high-performance liquid chromatographic determination of diclofenac in microdialysis samples.

High-performance liquid chromatography (HPLC) was used to analyze microdialysis samples obtained in vivo from human subcutaneous adipose tissue after topical application of the nonsteroidal anti-inflammatory drug diclofenac. For the reliable determination of diclofenac two different detection principles were applied in two different laboratories. One HPLC method utilized UV-detection at 280 nm, the other one used selected reaction monitoring mass spectrometry (MS).