DIBEKACIN CONCENTRATION IN VARIOUS TISSUES OF PATIENTS

Abstract

Dibekacin, 3, 4-dideoxy-kanamycin B (DKB), for intramuscular injection was tested in 38 patients who were hospitalized with acute or subacute abdominal infectious diseases. They were 19 appendicitis, 8 appendicitis with perforative panperitionitis, 7 cholelithiasis with cholecystitis, 1 cholangiolitic hepatitis and 3 other diseases (gastric ulcer, left thyroid cancer and left lower leg thromboangitis obliterans). Tissue specimens of different places and plasma samples were taken during the operation from removed organs. Weight of specimens was at least over 3g. Determination of DKB concentration was performed according to the bioassay method (bioassay with Bacillus subtilis ATCC 6633 strain). In the appendicitis DKB concentrations in the appendixes were directly proportional to the degree of pathological inflammatory changes. The DKB concentrations of bile in gall bladder were higher than those in bile duct. In a gastric ulcer patient, DKB concentrations of gastric wall and appendix were trace. INTRODUCTION In the chemotherapy of the infectious diseases, it is very important to know minimal inhibitory concentration (MIC) of the drug for the pathogenic bacteria and affinity of the drug for the inflammatory object organ or tissues. We usually substitute the measurements of clinical blood concentration of drug for those of the object tissue itself 1). The tissue concentration was directly measured from the experimental animal tissue. However. it is difficult to speculate human tissue concentration from experimental animal studies because of the pathological changes of inflammatory tissue and microcirculation of local regions. The data measuring the concetration of antibiotics in the human infectious tissue are very few. The present study, therefore, was performed to determine the concentration of antibiotics in infectious tissues of human beings, using DKB as test sample. MATERIAL AND METHOD An antibiotic drug of aminoglycoside group, dibekacin (DKB) for intramuscular injection was. used. The patients were 38 cases ; 21 cases female and 17 male. DKB in a dose of 100 mg was given by intramuscular injection 30 minutes before operation. Tissue specimens of different places and plasma samples were taken during the operation from removed organs. Weight of specimens was at least over 3g. The plasma samples were taken when the removed organ was clamped to stop blood flow. The removed organs were washed in saline and frozen at -20•Ž. The materials were preserved at -20°C. for shipment. The specimens and plasma samples (kept at -20•Ž) were sent to the Pharmaceutical Development Laboratories, Meiji Seika Kaisha Ltd. (Kawasaki City, Japan). The tissue specimens were added 0.1 M phosphate buffer solution (pH 8. 0), and then were broken into pieces and homogenized. These homogenates were centrifugated at 3000 rpm for 20 minutes. Determina ion of DKB concentration in the supernatant was performed according to the bioassay method (Bioassay with Bacillus subtilis ATCC 6633. strain) 6).