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 mesylates of four dihydrogenated ergot alkaloid derivatives (dihydroergocornine, dihydroergocristine, alpha-dihydroergocryptine and beta-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 x 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 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 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.
Setnikar
I
I
Scientific Department, Rotta Research Laboratorium, Monza, Italy. ivo.setnikar@rotta.com
Schmid
K
K
Rovati
L C
LC
Vens-Cappell
B
B
Mazur
D
D
Kozak
I
I
D000328:Adult; D019540:Area Under Curve; D001682:Biological Availability; D001702:Biopharmaceutics; D018592:Cross-Over Studies; D004088:Dihydroergotoxine / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D006801:Humans; D008297:Male; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D019999:Pharmaceutical Solutions; D013607:Tablets
D018696:Neuroprotective Agents; D019999:Pharmaceutical Solutions; D013607:Tablets; D004088:Dihydroergotoxine