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Correlation of haloperidol levels between submandibular saliva and brain in the rat
Noriyasu Takai1, Kenji Eto, Kenji Uchihashi
1Department of Physiology, Osaka Dental University, 8-1, Kuzuha-hanazono-cho, Hirakata, Osaka 573-1121, Japan. takai@cc.osaka-dent.ac.jp
Objective:
The clinical usefulness of therapeutic drug monitoring (TDM) for haloperidol using blood samples has to be validated. Despite the potential advantage of TDM using saliva, there are few reports comparing drug levels in saliva and blood. Additionally, the relation between haloperidol levels in saliva and brain, the target organ of this drug, has not been reported. We compared haloperidol levels in rat submandibular saliva, plasma and brain.
Design:
Haloperidol was administered through the femoral vein (0.25 mg/kg). Submandibular saliva was collected 30 min after drug administration. To stimulate secretion, the chorda (parasympathetic) and superior cervical ganglion (sympathetic) were electrically stimulated, and pilocarpine was administered. The concentration of haloperidol in saliva, plasma and brain homogenate was determined.
Results:
Haloperidol levels in saliva elicited by any stimuli significantly correlated with levels in the brain and plasma. The correlation of haloperidol between saliva and brain was higher than that between plasma and brain. Immunohistochemistry showed that haloperidol was secreted from striated duct cells within the submandibular gland.
Conclusion:
These results suggested that haloperidol was specifically secreted from the striated duct system, and that salivary drug levels reflect the levels in the brain more precisely than plasma.
