Aims To investigate the peripheral vascular effects and pharmacokinetics of
dihydroergotamine (DHE) 0.5 mg after a single subcutaneous administration
in humans.
Methods A double-blind, placebo-controlled cross-over study was performed i
n 10 healthy male subjects. A wash-out period of 2 weeks separated the two
study periods. During each period, just before and at regular intervals aft
er drug administration, vascular measurements were performed and venous blo
od samples were drawn. Vessel wall properties were assessed at the brachial
artery, by ultrasound and applanation tonometry. Blood pressure and heart
rate were recorded with an oscillometric device. Forearm blood flow was mea
sured with venous occlusion plethysmography. For all parameter-time curves
the area under the curve (AUC) was calculated. Differences in AUC after pla
cebo and DHE (Delta AUC) were analysed and the time-course of the differenc
e assessed. DHE pharmacokinetics were analysed according to a two-compartme
nt open model with an absorption phase.
Results AUC for blood pressure, heart rate and forearm vascular resistance
did not change after DHE. Brachial artery diameter and compliance decreased
(P < 0.01); Delta AUC (95% confidence interval) equalled -8.81 mm h (-12.9
7/-4.65) and -0.98 mm(2) kPa(-1) h (-1.61/-0.34), respectively. Diameter de
creased (P < 0.05) from 1 until 24 h after DHE (peak decrease 9.7% at 10 h)
; compliance from 2 until 32 h (24.8% at 2 h). Time to reach maximum plasma
concentration of DHE averaged 0.33 +/- 0.08 h (+/- s.e.mean); terminal hal
f-life was 5.63 +/- 1.15 h.
Conclusions DHE decreased diameter and compliance of the brachial artery wh
ereas forearm vascular resistance remained unchanged. Thus, DHE acts on con
duit arteries without affecting resistance arteries. Furthermore, a discrep
ancy was demonstrated between the plasma concentrations of DHE which rapidl
y reach peak levels and quickly decline, and its long lasting vasoconstrict
or activity.