Host: The Japanese Society of Toxicology
Name : The 50th Annual Meeting of the Japanese Society of Toxicology
Date : June 19, 2023 - June 21, 2023
Intrathecal (IT) dosing is a useful technique that enables drug delivery without being affected by the blood-brain barrier. To establish the IT dosing method by lumbar puncture in rats, we conducted a comparative study under various dosing conditions. Using male Sprague-Dawley rats (7-8 weeks old), a needle was inserted between the fifth and sixth lumbar vertebrae under isoflurane anesthesia, and after confirming the tail flick, 50 µL/body of 10 mg/mL inulin was dosed. Thirty minutes after dosing, cerebrospinal fluid (CSF) was collected from the cisterna magna under isoflurane anesthesia, and inulin concentration was measured by ELISA. We compared the dosing rate (bolus or infusion) and the body position at dosing (prone or standing position). In addition, the animals were dosed twice at 1 week interval, and the concentration difference within individuals was assessed. The condition of the animals after dosing was also checked. High inulin concentrations (>300 µg/mL) were observed in 6/9 animals with bolus and 2/12 animals with infusion in the prone position. Bolus dosing in the standing position succeeded in 10/20 animals. In the multiple dose experiment, the high inulin exposure was observed in 4/10 animals in the first dosing and 8/10 animals in the second dosing, suggested a large difference in inulin concentration even in the same animal. None of the animals showed any abnormality after dosing. These results suggest that the drug concentration in the cisterna magna CSF may be affected by the dosing rate and body position during IT dosing by lumbar puncture in rats.
