[Experimental studies on tissue distribution of 14C-labelled antimicrobial agent in the otorhinolaryngological field--application of macro-autoradiography].
The distribution of antimicrobial agents in infected target tissues would be essential for their application to treat the sites of infection. Taking accounts of the view point, we had reported the distribution of 3 nalidixic acid analogs in tissues which are related to otorhinolaryngology by macro-autoradiography and radiometry. We investigated here in the distribution of a nalidixic acid analog OPC-7241. This agent is 9-fluro-5-methyl-8-(4-methyl-1-piperaginyl)-6, 7-dihydro-1-oxo-1H, 5H-benzo [ij]quinoligine-2-carboxylic acid supplied by Otsuka Pharmaceutical Co., Ltd. Autoradiography was performed 30 minutes after intravenous administration of 14C-OPC-7241 in 2.96 MBq(80.0 microCi)/12.5mg/kg to New Zieland White rabbit. Radiometry was performed 30 minutes, 1 hour and 3 hours after intravenous administration of 14C-OPC-7241 in 740 kBq (20.0 microCi)/10.0 mg/kg to NZW rabbits. Such care was taken in filling the carboxymethyl cellulose paste into the paranasal cavity, nasal cavity, oral cavity and external ear canal not to damage mechanically. Horizontal frozen sections parallel to mandibular basis were cut in 50 microns thickness in a cryostadt. Blackening of 14C-OPC-7241 was most significant in soft palate and its expanse which is apparently the same gland-like tissues as soft palate when stained with hematoxylin and eosin. Significant radioactivity was recognized in tonsils, the cartilage of external ear canal, septal cartilage, periodontal membrane, dental pulp, muscle and concha nasalis ventralis. The levels was low in ethmoid cells, mucosa of tympanic cavity, cochlea, maxillary sinus and bone. Quantitatively, the levels of 14C-OPC-7241 radioactivity were high in soft palate, mandibular gland and tonsils. Radioactivity was significant in tongue and concha nasalis ventralis. The levels were low in turbinates, ethmoid cells, maxillary sinus, septal cartilage, septal mucosa, cochlea, brain, optic nerve and lens. Thus radiometric results agreed with the above autoradiographic findings. Macro-autoradiography can be one of useful means for the evaluation chemotherapeutic agents for possible clinical application.
D000818:Animals; D000900:Anti-Bacterial Agents / Q000378:metabolism*; D001345:Autoradiography / Q000379:methods*; D002250:Carbon Radioisotopes; D004423:Ear / Q000378:metabolism*; D007830:Larynx / Q000378:metabolism*; D009268:Nalidixic Acid / Q000378:metabolism; D009297:Nasal Mucosa / Q000378:metabolism*; D011817:Rabbits; D014018:Tissue Distribution
D000900:Anti-Bacterial Agents; D002250:Carbon Radioisotopes; D009268:Nalidixic Acid