Fundamental studies on intravesical instillation of carboquone for treatment of urinary bladder tumors--on the effects of intravesical instillation of carboquone in normal beagle dogs

CQの膀胱内注入療法による副作用の発生につきMMCを対照薬とし雌性Beagle犬を用いCQ 5mgと10mgの投与量で膀胱内注入実験をおこなった.(1)空置膀胱内へCQ 10mg/20ml PBSの48時間貯留実験で, CQによる膀胱壁全層に炎症性変化が発生したが, 全身的副作用の発生は認めなかった.溶解液PBSには局所的, 全身的副作用を認めなかった.(2) CQ 5mg/20ml PBSを週1回, 3週間3回膀胱内注入実験で, 注入終了後3週間の実験終了時には, 血液, 血液化学的諸検査結果に変化はみず, 膀胱局所は内視鏡的には回復傾向がいちじるしく, 粘膜下組織に軽度の炎症性細胞浸潤をみ, 3頭中2頭に筋層と漿膜層に浮腫と軽度の炎症性変化を認めたのみであった.膀胱粘膜上皮には再生過程と考えられる粘膜上皮過形成をみた.(3) MMC 10mg/20ml PBSを週1回, 3週間3回膀胱内注入群では, 3頭中2頭で, 注入終了後7日目に未梢血白血球数が若干減少したが, 実験終了時には正常値に回復していた.膀胱鏡所見は3頭中1頭は回復傾向をみたが, 他の2頭では, 膀胱鏡所見, 病理組織学的所見ともにいちじるしい炎症性変化を認めた
The effects of intravesical instillation of Carboquone at the clinically used doses of 5 and 10 mg on the normal mucosa of female beagle dogs was compared with that of 10 mg Mitomycin C used as the control drug. Intravesical instillation for 48 hours of 10 mg carboquone/20 ml phosphate buffer solution (PBS) after bilateral cutaneous uretrostomies produced severe inflammatory changes in all layers of the bladder wall. However, no secondary effects were observed in blood laboratory examinations or histological examinations of the whole organ after autopsy. Phosphate buffer solution produced no remarkable secondary effects in animals. Five milligrams carboquone per 20 ml PBS was instilled intravesically once a week for 3 weeks in normal animals. Cystoscopically , the bladder mucosa recovered normally. Blood laboratory examinations showed no abnormal results, but the bladder epithelium had regenerative epithelial hyperplasia and slightly inflammatory changes in the submucosal layers. Two of the three control animals given instillation of 10 mg of Mitomycin C/20 ml PBS had slight leucopenia at 7 days after the last intravesical instillation, but leucocyte count was normal at the end of the experiment. Cystoscopic and histological examination of the epithelium of the urinary bladder revealed severe inflammatory changes in 2 of the 3 animals.