Pharmacokinetic Characterization of Dehydroevodiamine in the Rat Brain

• Published in: Journal of pharmaceutical sciences Vol. 93; no. 2; pp. 283 - 292
• Main Authors: Ahn, Sung‐Hoon, Jeon, Seng‐Ho, Tsuruo, Takashi, Shim, Chang‐Koo, Chung, Suk‐Jae
• Format: Journal Article
• Language: English
• Published: Hoboken Elsevier Inc 01.02.2004; Wiley Subscription Services, Inc., A Wiley Company; Wiley; American Pharmaceutical Association
• Subjects: Algorithms; Alkaloids - blood; Alkaloids - cerebrospinal fluid; Alkaloids - pharmacokinetics; Alzheimer's disease; Animals; Area Under Curve; Biological and medical sciences; blood-brain barrier; blood-cerebrospinal fluid barrier; Brain - metabolism; brain distribution; Cell Line; Cholinesterase Inhibitors - blood; Cholinesterase Inhibitors - cerebrospinal fluid; Cholinesterase Inhibitors - pharmacokinetics; Chromatography, High Pressure Liquid; dehydroevodiamine; immortalized mouse brain capillary endothelial cells; Injections, Intravenous; Magnetic Resonance Spectroscopy; Male; Medical sciences; Miscellaneous; Neuropharmacology; Pharmacology. Drug treatments; Rats; Rats, Sprague-Dawley; Spectrophotometry, Ultraviolet; brain distribution; blood–cerebrospinal fluid barrier; immortalized mouse brain capillary endothelial cells; blood–brain barrier; Alzheimer's disease; dehydroevodiamine; Biological fluid; Endothelial cell; Rat; Alzheimer disease; Blood brain barrier; Blood; Encephalon; Degenerative disease; blood-brain barrier; Nervous system diseases; Rodentia; Antialzheimer agent; Cerebral disorder; Vertebrata; Mammalia; blood-cerebrospinal fluid barrier; Mouse; Animal; Central nervous system disease; Distribution; Pharmacokinetics
• ISSN: 0022-3549; 1520-6017
• DOI: 10.1002/jps.10546

The objective of this study was to examine the kinetics of the distribution of dehydroevodiamine (DHED) in the rat brain. After an intravenous infusion of 15min (dose of 1–10mg/kg), the temporal profiles of the plasma levels of DHED declined in a multiexponential manner. Moment analysis indicated that the clearance and steady‐state volume of distribution for DHED were not statistically different with the dose, indicating that the pharmacokinetics for DHED is linear in the range examined. Nonlinear regression analysis of DHED concentrations in the plasma and the brain revealed that the linear kinetics into and out from the brain reasonably described the data and that the clearances for influx into and efflux from the brain were comparable. Transport clearances for DHED across MBEC4 monolayers, an in vitro model of the blood–brain barrier, were also comparable for influx and efflux, and were independent of the medium concentration. The concentration of DHED in cerebrospinal fluid was negligible compared with that found in plasma, indicating that the drug is not primarily distributed to the brain via the blood–cerebrospinal fluid barrier. These observations indicate that DHED is transported from the systemic circulation to the brain via the blood–brain barrier by linear kinetics. © 2004 Wiley‐Liss, Inc. and the American Pharmacists Association J Pharm Sci 93:283–292, 2004