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Dihydroergotamine: discrepancy between arterial, arteriolar and pharmacokinetic data
J N de Hoon1, K A Poppe, H H Thijssen
1Department of Pharmacology and Toxicology, Cardiovascular Research Institute Maastricht, Maastricht University, Maastricht, The Netherlands. Jan.deHoon@uz.kuleuven.ac.be
British Journal of Clinical Pharmacology
|July 17, 2001
Summary
Dihydroergotamine (DHE) reduced brachial artery diameter and compliance but not forearm vascular resistance. This indicates DHE affects larger arteries, with a delayed vasoconstrictor effect compared to plasma levels.
Area of Science:
- Pharmacology
- Vascular Physiology
- Clinical Pharmacology
Background:
- Dihydroergotamine (DHE) is used for migraine treatment.
- Understanding its peripheral vascular effects is crucial for safe and effective use.
Purpose of the Study:
- To investigate the peripheral vascular effects of a single subcutaneous dose of dihydroergotamine (DHE) 0.5 mg.
- To determine the pharmacokinetics of DHE in healthy human subjects.
Main Methods:
- A double-blind, placebo-controlled, cross-over study in 10 healthy males.
- Vascular measurements (brachial artery diameter, compliance, blood pressure, heart rate, forearm blood flow) and blood sampling were performed.
- Pharmacokinetics analyzed using a two-compartment open model.
Main Results:
- Dihydroergotamine (DHE) significantly decreased brachial artery diameter and compliance.
- No significant changes were observed in blood pressure, heart rate, or forearm vascular resistance.
- DHE exhibited rapid peak plasma concentrations and a terminal half-life of approximately 5.6 hours.
Conclusions:
- DHE exerts vasoconstrictor effects on conduit arteries (brachial artery) but not resistance arteries (forearm).
- A dissociation exists between DHE's rapid plasma decline and its prolonged vasoconstrictor activity.
- Findings suggest DHE's vascular effects are artery-specific and longer-lasting than indicated by plasma levels.