Tissue and fluid penetration of garenoxacin in surgical patients.

Background and Purpose: Garenoxacin is a novel des-F(6)-quinolone that exhibits broad-spectrum activity against a wide range of aerobic and anaerobic pathogens of clinical importance. This study examined the penetration of garenoxacin into sinus mucosa, incisional skin, subcutaneous tissue, bile, adipose tissue, striated muscle, bone, gallbladder wall, liver, small and large bowel mucosa, and mesenteric lymph nodes relative to the plasma concentration after an oral 600 mg dose.
Methods: A series of 30 patients, ages 20 to 83 years, undergoing elective surgery were enrolled. Patients received a single 600 mg oral dose of garenoxacin before surgery. Blood and tissue specimens were collected at surgery 3-5 h post-dose, and garenoxacin concentrations were determined using validated liquid chromatography/tandem mass spectrometry assays designed specifically for each tissue and biofluid.
Results: The mean plasma or bile (mcg/mL) and tissue (mcg/g) concentrations ( +/- standard deviation) were plasma 5.71 +/- 3.44, bile 7.59 +/- 9.96, adipose tissue 0.90 +/- 0.54, subcutaneous tissue 1.19 +/- 1.23, incisional skin 3.06 +/- 1.74, striated muscle 3.92 +/- 2.54, bone 2.82 +/- 2.42, sinus mucosa 5.26 +/- 3.84, liver 1.84 +/- 0.75, gallbladder 11.59 +/- 11.94, large intestine 12.13 +/- 9.34, small intestine 15.66 +/- 19.20, and mesenteric lymph node 3.10 +/- 2.44.
Conclusion: After a single 600 mg oral dose, garenoxacin penetrates well into selected tissues and fluids. In addition, the tissue and fluid concentrations at 3-5 hours post-dose exceeded the minimum inhibitory concentration-90% of most targeted pathogens, suggesting that garenoxacin would be effective in the treatment of sinus, skin and skin structure, and intra-abdominal infections.