Evaluation of calcitonin gene-related peptide prolonged release tablet in vitro and in vivo

Calcitonin gene related-peptide (CGRP) has been known as one of the most potent vasodilator, containing in perivascular nerves innervating arteries. We previously reported that human α-CGRP (hCGRP) could dilate the spastic cerebral arteries after experimental subarachnoid hemorrhage(SAH) in rabbits. The vasodilatory effect of hCGRP, however, did not continue up to 6 hours after treatment. In the present study, we investigated a prophylactic potential of sustained higher cerebrospinal fluid (CSF) level of hCGRP at least 5 days. For this problem, hCGRP prolonged-release tablet (hCGRP tab.) was prepared. The hCGRP tab. was composed of hydroxypropylcellulose, lactose, hydrogenated oil, stearic acid and hCGRP. These materials were mixed and compressed by tabletting machine to form a tablet of 2 mm thickness and 6 mm diameter, weighing 60 mg. The release of hCGRP from the tablets was detected in vitro and in vivo using HPLC and radioimmunoassay (RIA), respectively. The tablet containing 24 μg hCGRP could slowly release approximately 80 % of its content with in the initial 5 days. The CSF level of rabbits of the hCGRP, the concentration of hCGRP in CSF before tablet implantation was below detectable limit. It was highest (23.1±18.36 nmol/l) 2 days after the implantation and remained detectable (3.08±2.67 nmol/l) until 5 days after the implantation. These results suggest that the hCGRP tab. release hCGRP over 5 days both in vitro and in vivo. This tablet may be clinically applicable in the treatment of patients with SAH against delayed vasospasm in man.