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

Beatriz Bicalho, Juliana Marconi Giolo, Sergio Lilla, Gilberto De Nucci

Department of Pharmacology, Faculty of Medical Sciences, UNICAMP, PO BOX 6111, 13084-971, Campinas - SP, Brazil.

Biopharmaceutics & drug disposition 2008 Jan

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Dihydroergotoxine is a mixture of semi-synthetic ergot alkaloids mainly used for age-related cognitive impairment. In this study, dihydroergotoxine (30 microM) was added to incubates of rat and bovine liver microsomes, and the resulting major metabolites were identified as hydroxy-dihydroergocornine, 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 microg/l. The peaks (C(max)) of their hydroxy-metabolites were 0.98, 0.53 and 0.30 microg/l, respectively. In conclusion, in this preliminary approach it was found that hydroxy-dihydroergocornine, hydroxy-dihydroergocryptine and hydroxy-dihydroergocristine were one order of magnitude higher in concentration than their parents in human plasma. 2007 John Wiley & Sons, Ltd

Citation

Beatriz Bicalho, Juliana Marconi Giolo, Sergio Lilla, Gilberto De Nucci. Identification and human pharmacokinetics of dihydroergotoxine metabolites in man: preliminary results. Biopharmaceutics & drug disposition. 2008 Jan;29(1):17-28