Correlation of haloperidol levels between submandibular saliva and brain in the rat

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...

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Bibliographic Details
Published in:Archives of oral biology 2006-07, Vol.51 (7), p.567-572
Main Authors: Takai, Noriyasu, Eto, Kenji, Uchihashi, Kenji, Yamaguchi, Masaki, Nishikawa, Yasuo
Format: Article
Language:English
Subjects:
Animals
Antipsychotic Agents - analysis
Antipsychotic Agents - blood
Antipsychotic Agents - pharmacokinetics
Brain
Brain Chemistry
Dentistry
Haloperidol
Haloperidol - analysis
Haloperidol - blood
Haloperidol - pharmacokinetics
Male
Plasma
Rat
Rats
Rats, Wistar
Saliva - chemistry
Salivation - drug effects
Submandibular Gland
Submandibular saliva
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Summary: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. 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. 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. 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.
ISSN:0003-9969
1879-1506
DOI:10.1016/j.archoralbio.2005.12.002