I. Setnikar, K. Schmid, L. Rovati
Jan 1, 2001
Citations
0
Influential Citations
12
Citations
Quality indicators
Journal
Arzneimittelforschung
Abstract
Summary Dihydroergotoxine mesylate (DHETM, CAS 8067\24-1), the combination of the mesylates of four dihydrogenated ergot alkaloid derivatives (dihydroergocornine, dihydroergocristine, α-dihydroergocryp tine and β-dihydroergocryptine), is used mainly for age - related cognitive impairment. The bioavailability of DHETM was investigated in a cross-over study on 20 male healthy volunteers to whom two single doses of 9 mg DHETM were administered either in tablets (Orphol® spezial) or in oral solution (Orphol® forte). DHETM was assayed in serum with a double radioimmunoassay method displaying a satisfactory cross-reactivity with the principal components of DHETM. After administration of tablets the peak of DHETM was (mean ± SE) 124 ± 16 pg/ml, the tmax 1.15 ± 0.21 h, the AUC 790 ± 93 pg/ml× h and the terminal elimination half-life 7.54 ± 1.23× h. After oral solution the peak of DHETM was 176 ± 16 pg/ml, the tmax 0.50 ± 0.04 h, the AUC 779 ± 94 pg/ml h and the terminal elimination half life 6.13 ± 0.76 h. The bioavailability of DHETM from tablets vs. that from oral solution differed only by a retard related to the dissolution time of DHETM from the tablets, but not for other pharmacokinetic parameters. The relatively high two single doses of 9 mg DHETM administered to the 20 subjects were well tolerated, causing only known and expected adverse reactions to DHETM (tiredness, headache and vertigo) that did not require discontinuation of the study.