2021 Volume 49 Issue 3 Pages 81-96
Purpose : Articaine hydrochloride is commonly used as a local anesthetic for dentistry in many countries. However, this compound has not been approved for use in Japan. To support the approval of articaine hydrochloride and adrenaline bitartrate (OKAD01) in Japan, we performed a phase Ⅰ clinical trial to clarify the pharmacokinetics and safety of injecting OKAD01 into the oral mucosae of healthy Japanese adults.
Methods : The subjects were healthy Japanese male adults. One (1.7 ml) or 3 cartridges (5.1 ml) of OKAD01 were injected into the oral mucosae of 6 subjects each. The blood concentration of articaine was measured before the injection and at 15 min, 30 min, 60 min, 2 h, 4 h, 12 h, and 24 h after the injection. Clinical laboratory tests and vital sign measurements were also performed, and adverse events were evaluated during this clinical trial.
Results : In the 1-cartridge trial, the maximum blood concentration (Cmax) and the time taken to reach it (Tmax) were 374.35±97.65 (252.7-514.5) ng/ml and 0.25±0.00 (0.25-0.25) h, respectively (mean±SD (minimum-maximum)). In the 3-cartridge trial, the Cmax and Tmax were 694.00±175.23 (517.9-970.4) ng/ml and 0.42±0.13 (0.25-0.5) h, respectively. Regarding adverse events, we encountered 1 case of headache in the 1-cartridge trial ; however, this event was not thought to be associated with the OKAD01 injection.
Conclusion : Injecting OKAD01 into the oral mucosae of healthy Japanese adults resulted in a Cmax of <5.0 μg/ml and did not cause any adverse events. This study demonstrated the safety and tolerability of OKAD01 in the Japanese population.
