Abstract
The absorption characteristics of dihydroergotoxine administered as an oral solution, tablet and retard capsule have been determined in a randomised cross-over investigation in 12 healthy males. The plasma concentrations of dihydroergotoxine produced by the three preparations, measured using a specific and sensitive radioimmuno-assay method over 24 h, exceeded 200 pg ml-1 for approximately 5 h and decayed in a biphasic manner with a slowest measured half-life of 12-14 h. The retard capsule differs from the other two preparations in having a low Cmax (50% of that recorded for the solution) and a clearly defined plateau. The bioavailability of the retard capsule was similar to that for the solution indicating that first-pass metabolism is not significantly increased following a three-fold prolongation in the absorption rate constant. The 20-40% greater bioavailability of dihydroergotoxine solution and retard capsule in comparison with the standard tablet may be due to a reduced contact time with gastric secretions achieved by means of rapid absorption from the stomach (solution) or delayed release at pH 1.5 (retard capsule).
Full text
PDF
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Aliache J. M., Briot M., Couquelet J., Vigo P. Comparative blood level of dihydroergotoxine (DHET) after administration of two oral forms (solution & tablet): a preliminary study. Eur J Drug Metab Pharmacokinet. 1981;6(3):221–224. doi: 10.1007/BF03189491. [DOI] [PubMed] [Google Scholar]
- Kiechel J. R., Lavène D., Humbert H., Guillaume M. F. Untersuchungen zur Bioverfügbarkeit von Hydergin spezial. Med Welt. 1982 Aug 27;33(34):1168–1170. [PubMed] [Google Scholar]
- Kopitar Z., Milovac J., Vrhovac B., Tadjer I. Comparison of the bioavailability of Redergin tablets (1.0 mg) and Redergin solution. Int J Clin Pharmacol Ther Toxicol. 1982 Mar;20(3):134–138. [PubMed] [Google Scholar]
- Loh W., Woodcock B. G. Spezifität und Präzision einer radioimmunologischen Bestimmung von Dihydroergotoxin im Plasma. Arzneimittelforschung. 1983;33(4):568–570. [PubMed] [Google Scholar]
- Meier J., Nüesch E., Schmidt R. Pharmacokinetic criteria for the evaluation of retard formulations. Eur J Clin Pharmacol. 1974 Oct 4;7(6):429–432. doi: 10.1007/BF00560355. [DOI] [PubMed] [Google Scholar]
- Schmidt R., Fanchamps A. Effect of caffeine on intestinal absorption of ergotamine in man. Eur J Clin Pharmacol. 1974;7(3):213–216. doi: 10.1007/BF00560383. [DOI] [PubMed] [Google Scholar]
- Woodcock B. G., Habedank W. D., Loh W., Rietbrock N. The ergoloid mesylate dihydroergotoxine: radioimmunoassay measurements on plasma and blood-pressure-lowering activity. J Cardiovasc Pharmacol. 1984 May-Jun;6(3):543–545. [PubMed] [Google Scholar]
- Woodcock B. G., Loh W., Habedank W. D., Rietbrock N. Dihydroergotoxine kinetics in healthy men after intravenous and oral administration. Clin Pharmacol Ther. 1982 Nov;32(5):622–627. doi: 10.1038/clpt.1982.212. [DOI] [PubMed] [Google Scholar]
- Zoglio M. A., Maulding H. V. Complexes of ergot alkaloids and derivatives. V. Interaction of methysergide maleate and caffeine in aqueous solution. J Pharm Sci. 1970 Dec;59(12):1836–1837. doi: 10.1002/jps.2600591229. [DOI] [PubMed] [Google Scholar]
- von Hattingberg H. M., Brockmeier D., Kreuter G. A rotating iterative procedure (RIP) for estimating hybrid constants in multi-compartment analysis on desk computers. Eur J Clin Pharmacol. 1977;11(5):381–388. doi: 10.1007/BF00566536. [DOI] [PubMed] [Google Scholar]