IRIKURA Mitsuru Kumamoto University, Graduate School of Pharmaceutical Sciences, Department of Clinical Chemistry and Informatics, Associate Professor, 大学院・薬学研究科, 助教授 (70151694)
IRIE Tetsumi Kumamoto University, Graduate School of Pharmaceutical Sciences, Department of Clinical Chemistry and Informatics, Professor, 大学院・薬学研究科, 教授 (60150546)
TANIGUCHI Masahiko Miyazaki Medical College, Department of Anesthesiology, Instructor, 医学部, 助手 (70305085)
|Budget Amount *help
¥8,100,000 (Direct Cost: ¥8,100,000)
Fiscal Year 2002: ¥4,500,000 (Direct Cost: ¥4,500,000)
Fiscal Year 2001: ¥3,600,000 (Direct Cost: ¥3,600,000)
Natural cyclodextrins and their derivatives have been administered intrathecally to improve solubility, to reduce systemic toxicity, or to enhance the bioavailability of drug properties. To evaluate their neurotoxicities, we administered sulfobutylether-beta-cyclodextrin, hydroxypropyl-beta-cyclodextrin, and maltosyl-beta-cyclodextrin at the concentration of 50, 125, and 250 mM, respectively, or 5 and 10% mannitols, or saline solution to the intrathecal space in rats, after that, observed neurological symptoms (death, convulsion, or irritation), tail flick latency, and histological lesion of the spinal cord. The results showed no neurological symptoms or histological abnormalities in rats that received with saline, sulfobutylether-beta-cyclodextrin at 50 mM, and maltosyl-beta-cyclodextrin at 50 and 125 mM, although some cyclodextrin derivatives and mannitols at various dosages produced neurological impairments and morphologic damage. Maltosyl-beta-cyclodextrin is the safest among three cyclodextrin derivatives administered intrathecally in this study.
We used 0.5 or 1% levobupivacaine complexed with maltosyl-beta-cyclodextrin at 100 mM for intrathecal and sciatic nerve blocks in rats. The anesthetic effects of levobupivcaine were prolonged 1.4〜2 times in both intrathecal and sciatic nerve blocks with no neurological impairments.