AIM:To investigate the bi-directional penetration of CPU-86017 across the BBB (Blood Brain Barrier) following iv and icv (intracerebroventricular) administration in mice.METHOD:The levels of CPU-86017 (p-Chlorobenzyltetrahydroberberine hydrochloride) in the brain, heart, kidney and blood of mice after acute administration of 3.0 mg/kg of CPU-86017 were measured by validated HPLC assay at several time points: 5, 10, 20, 30 and 60 minutes. RESULT:The maximum concentrations of CPU-86017 in the brain, heart, kidney and plasma achieved at 10 minutes by both routes of administration were 0.83±0.335, 25.13±4.17, 56.0±19.69, and 2.23±0.97 μg/ml in the iv group and 23.68±4.2,15.9±10.24, 7.93±4.68 and 3.32±2.3 μg/ml in the icv group, respectively. The decline in concentrations was rapid in plasma. The highest concentration of CPU-86017 was found in the kidney (56.0±19.69 μg/g) after iv administration and in the brain (23.68±4.2 μg/g) after icv injection. The difference in concentrations in the kidney and heart was not significant at 60 min after iv administration. Given by icv administration CPU-86017 reached the peripheral tissues and plasma at each of the five time points, whereas by the iv route at 20, 30 and 60 min the drug could not be detected in the brain.CONCLUSION:The permeability of CPU-86017 through the BBB was well established by two ways: blood circulation to the brain and brain to general circulation. However, a big difference exists between these ways. It is more difficult to penetrate from the blood to the brain than from brain to the peripheral.