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European Journal of Clinical Pharmacology

, Volume 41, Issue 6, pp 597–602 | Cite as

Pharmacokinetic investigation of oral and IV dihydroergotamine in healthy subjects

  • P. A. Wyss
  • J. Rosenthaler
  • E. Nüesch
  • W. H. Aellig
Originals

Summary

A new radioimmunoassay (RIA) for the specific measurement of dihydroergotamine (DHE), sufficiently sensitive for the determination of low plasma concentrations, has been used to investigate the pharmacokinetics of unchanged DHE. In a randomized crossover trial, eight healthy male volunteers received single doses of DHE 5 mg, 10 mg and 20 mg orally and 0.1 mg and 0.5 mg intravenously. It was possible to determine plasma concentrations and urinary excretion of DHE over the following 48 h. A long terminal plasma elimination phase of unchanged DHE (half-life 15 h) was found. A similar terminal elimination half-life was also calculated from urine data. The multi-exponential decline in plasma DHE with a long terminal half-life suggests that distribution into a deep compartment contributes to the long-lasting effect of the drug. Plasma protein binding was 93%. Despite extensive tissue distribution (Vz=33 l/kg) and a high plasma clearance (CLP=2l/min), dose-independent linear pharmacokinetics was observed. The present assay was at least 20-times more specific than the polyvalent RIA used previously and appears suitable to explore the pharmacokinetics of unchanged DHE in patients on low-dose therapy. The long terminal elimination half-life of DHE only reported previously in studies using 3H-labelled drug, and considered to be due to metabolites, was also true for the parent compound. This, in addition to the sustained pharmacological activity of the 8′-hydroxy metabolite already shown, provides a further explanation for the long duration of action of DHE in animals and man.

Key words

Dihydroergotamine mesilate pharmacokinetics urinary excretion prolonged half-life deep compartment RIA adverse effects 

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Copyright information

© Springer-Verlag 1991

Authors and Affiliations

  • P. A. Wyss
    • 1
  • J. Rosenthaler
    • 2
  • E. Nüesch
    • 3
  • W. H. Aellig
    • 3
  1. 1.Division of Clinical Toxicology and Environmental Medicine, Department of Internal Medicine, Medical College of VirginiaVirginia Commonwealth UniversityRichmondUSA
  2. 2.Biopharmaceutical DepartmentSandoz Pharma Ltd.BaselSwitzerland
  3. 3.Clinical Research DepartmentSandoz Pharma Ltd.BaselSwitzerland

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