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(Reference retrieved automatically from Google Scholar through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Identification and human pharmacokinetics of dihydroergotoxine metabolites in man: preliminary results

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Author(s):
Bicalho‚ B. ; Giolo‚ J.M. ; Lilla‚ S. ; De Nucci‚ G.
Total Authors: 4
Document type: Journal article
Source: BIOPHARMACEUTICS & DRUG DISPOSITION; v. 29, n. 1, p. 17-28, 2008.
Abstract

Dihydroergotoxine is a mixture of semi-synthetic ergot alkaloids mainly used for age-related cognitive impairment. In this study, dihydroergotoxine (30 mu M) was added to incubates of rat and bovine liver microsomes, and the resulting major metabolites were identified as hydroxydihydroergocornine, hydroxy-dihydroergocryptine and hydroxy-dihydroergocristine on the basis of molecular mass measurements, determined with a time-of-flight mass spectrometer. The relevance of these to humans was then investigated by simultaneously monitoring dihydroergotoxine and its hydroxy-metabolites in human plasma by LC-MS/MS after oral dosing of dihydroergotoxine mesylate (27 mg) to a healthy volunteer (male, age 45, height 1.93 m, weight 103 kg). In this preliminary approach, the peaks (C-max) of dihydroergocornine, dihydroergocryptine and dihydroergocristine were about 0.04 mu g/l. The peaks (C-max) of their hydroxy-metabolites were 0.98, 0.53 and 0.30 mu g/l, respectively. In conclusion, in this preliminary approach it was found that hydroxy-dihydroergocornine, hydroxydihydroergocryptine and hydroxy-dihydroergocristine were one order of magnitude higher in concentration than their parents in human plasma. Copyright (C) 2007 John Wiley & Sons, Ltd. (AU)

FAPESP's process: 05/04792-2 - First phase metabolism of ergot derivatives used in the treatment of Alzheimer's Disease
Grantee:Beatriz Bicalho
Support Opportunities: Scholarships in Brazil - Post-Doctoral