Bioavailability and pharmacokinetic profile of dihydroergotoxine from a tablet and from an oral solution formulation

Dihydroergotoxine mesylate (DHETM, CAS 8067-24-1), the combination of the m esylates of four dihydrogenated ergot alkaloid derivatives (dihydroergocorn ine, dihydroergocristine, alpha -dihydroergocryptine and beta -dihydroergoc ryptine), is used mainly for age-related cognitive impairment. The bioavail ability 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(R) spezial) or in oral solution (Orphol(R) forte). DHETM was assayed in serum with a double radioimmunoassay method displaying a sa tisfactory cross-reactivity with the principal components of DHETM. After administration of tablets the peak of DHETM was (mean +/- SE) 124 +/- 16 pg/ml, the t(max) 1.15 +/- 0.21 h, the AUC 790 +/- 93 pg/ml x h and the terminal elimination half-life 7.54 +/- 1.23 h. After oral solution the pe ak of DHETM was 176 +/- 16 pg/ml, the t(max) 0.50 +/- 0.04 h, the AUC 779 /- 94 pg/ml x 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 s ubjects were well tolerated, causing only known and expected adverse reacti ons to DHETM (tiredness, headache and vertigo) that did not require discont inuation of the study.