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Tissue and fluid penetration of garenoxacin

Abstract number: 1134_02_291

Wang Z., Edmiston C., Rolston K.V., Grasela D., Gajjar D.

Objective:

Garenoxacin (GRN) is a novel des-F(6)-quinolone being developed for a variety of indications because of its efficacy against a broad spectrum of pathogens, including anaerobes. The objective of this study was to assess the tissue or fluid to plasma ratios of GRN following a single oral dose.

Method:

An open-label study was conducted in subjects >=18 years of age with a body mass index <=33 kg/m2 undergoing abdominal surgical procedures that would permit the removal of tissue or fluid without increased risk to the subject. A single 600 mg oral dose of GRN was administered based on the scheduled operative time. The tissue or fluid (with corresponding plasma sample) was collected 3 to 5 hours post-dose. Concentrations of GRN in biological fluids and tissues were determined using validated LC/MS/MS assays. Safety was assessed by measurement of vital signs, physical examination, and electrocardiographic and clinical laboratory evaluations. Adverse event (AE) monitoring was performed from time of consent until discharge from the study.

Results:

Thirty-one subjects were enrolled in and completed the study. Mean fluid or tissue GRN concentrations greater than that found in plasma (mean fluid or tissue to plasma ratio >1) occurred in large and small bowel tissue, gallbladder, and liver. Mean fluid or tissue GRN concentrations less than that found in plasma occurred in adipose tissue, bone, sinus mucosa, striated muscle, incisional skin, and subcutaneous tissue. Mean GRN concentrations in bile and lymph node tissue were roughly similar to that found in plasma. Tissue and fluid concentrations of GRN exceeded the MIC90 of most target organisms involved in skin and soft tissue, bone, and intra-abdominal infections and sinusitis >=2-fold. No treatment-emergent AEs or serious AEs were considered to be related to GRN.

Conclusion:

A 600 mg oral dose of GRN penetrates well into most of the tissues and fluids studied, with concentrations exceeding the MIC90 of most pathogens causing sinusitis, skin and soft tissue infections, bone infections, and intra-abdominal infections. These results suggest that adequate concentrations of GRN can be achieved to treat infections at these sites.

Session Details

Date: 01/08/2007
Time: 00:00-00:00
Session name: XXIst ISTH Congress
Subject:
Location: Oxford, UK
Presentation type:
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