[Intrathecal perfusion of ACNU neurotoxicity and intrathecal pharmacokinetics in dogs]. 1989

M Kochi, and J Kuratsu, and Y Mihara, and N Inoue, and S Takaki, and N Sueyoshi, and N Soyama, and S Uemura, and Y Ushio
Department of Neurosurgery, Kumamoto University Medical School, Japan.

We studied the feasibility of intrathecal ACNU perfusion therapy against subarachnoid dissemination of malignant glioma. Intrathecal perfusion was performed in adult dogs by constant drip administration of 1 to 2 mg ACNU dissolved in 10 to 20 ml of lactate Ringer solution into the lateral ventricle and cerebrospinal fluid drainage through the lumbar puncture. The perfusion time was changed from 15 to 71 min. A bolus injection of 2 mg ACNU was also tested in one dog. No neurological symptom was noted during and after perfusion, and histological examination reveal only a minimum denudation of ependyma in a small area. Concentration of ACNU in CSF and serum were measured by HPLC (high-performance liquid chromatography). ACNU was detected in lumbar CSF only by perfusion, not by bolus injection, and the maximum concentrations were 6.26 to 25.76 micrograms/ml. The elimination phase of ACNU in lumbar CSF followed linear kinetics and the half-time was 18 min on average. AUCs (area under the drug concentration-time curve) were 346 to 896 micrograms.min/ml and they were the equivalent of in vitro cell kills in excess of 3 logs for rat 9L gliosarcoma and human glioma 126 cells. Serum concentration was 0.10 micrograms/ml in maximum. These findings suggest the feasibility of intrathecal ACNU perfusion therapy against subarachnoid dissemination of malignant glioma and warrant further studies.

UI MeSH Term Description Entries
D009420 Nervous System The entire nerve apparatus, composed of a central part, the brain and spinal cord, and a peripheral part, the cranial and spinal nerves, autonomic ganglia, and plexuses. (Stedman, 26th ed) Nervous Systems,System, Nervous,Systems, Nervous
D010478 Chemotherapy, Cancer, Regional Perfusion Neoplasm drug therapy involving an extracorporeal circuit with temporary exclusion of the tumor-bearing area from the general circulation during which high concentrations of the drug are perfused to the isolated part. Cancer Chemotherapy, Regional Perfusion,Perfusion Cancer Chemotherapy, Regional,Regional Perfusion Antineoplastic Chemotherapy,Isolation Perfusion Cancer Chemotherapy,Regional Perfusion Cancer Chemotherapy
D002851 Chromatography, High Pressure Liquid Liquid chromatographic techniques which feature high inlet pressures, high sensitivity, and high speed. Chromatography, High Performance Liquid,Chromatography, High Speed Liquid,Chromatography, Liquid, High Pressure,HPLC,High Performance Liquid Chromatography,High-Performance Liquid Chromatography,UPLC,Ultra Performance Liquid Chromatography,Chromatography, High-Performance Liquid,High-Performance Liquid Chromatographies,Liquid Chromatography, High-Performance
D004285 Dogs The domestic dog, Canis familiaris, comprising about 400 breeds, of the carnivore family CANIDAE. They are worldwide in distribution and live in association with people. (Walker's Mammals of the World, 5th ed, p1065) Canis familiaris,Dog
D004805 Ependyma A thin membrane that lines the CEREBRAL VENTRICLES and the central canal of the SPINAL CORD. Ependymas
D006207 Half-Life The time it takes for a substance (drug, radioactive nuclide, or other) to lose half of its pharmacologic, physiologic, or radiologic activity. Halflife,Half Life,Half-Lifes,Halflifes
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D013116 Spinal Cord A cylindrical column of tissue that lies within the vertebral canal. It is composed of WHITE MATTER and GRAY MATTER. Coccygeal Cord,Conus Medullaris,Conus Terminalis,Lumbar Cord,Medulla Spinalis,Myelon,Sacral Cord,Thoracic Cord,Coccygeal Cords,Conus Medullari,Conus Terminali,Cord, Coccygeal,Cord, Lumbar,Cord, Sacral,Cord, Spinal,Cord, Thoracic,Cords, Coccygeal,Cords, Lumbar,Cords, Sacral,Cords, Spinal,Cords, Thoracic,Lumbar Cords,Medulla Spinali,Medullari, Conus,Medullaris, Conus,Myelons,Sacral Cords,Spinal Cords,Spinali, Medulla,Spinalis, Medulla,Terminali, Conus,Terminalis, Conus,Thoracic Cords
D015376 Nimustine Antineoplastic agent especially effective against malignant brain tumors. The resistance which brain tumor cells acquire to the initial effectiveness of this drug can be partially overcome by the simultaneous use of membrane-modifying agents such as reserpine, calcium antagonists such as nicardipine or verapamil, or the calmodulin inhibitor, trifluoperazine. The drug has also been used in combination with other antineoplastic agents or with radiotherapy for the treatment of various neoplasms. ACNU,NSC 245382

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