The pharmacokinetics of subcutaneous dihydroergotamine with and without a dextran 70 infusion

Summary

The pharmacokinetics of subcutaneous dihydroergotamine (DHE) with or without dextran 70 infusion was evaluated in a single- and multiple-dose study in 30 patients. Radioimmunoassay was used to measure plasma DHE and the anthrone method to determine the dextran concentration. In the single-dose study no significant interaction between DHE and dextran was noted with respect to their plasma levels. The absorption of s.c. DHE was rapid and the disappearance curve followed a biphasic pattern, t_0.5 α being 1.4 and 2.0 h, t_0.5 β 22 and 21 h for DHE and DHE/dextran 70, respectively. In the multi-dose study the trough level of DHE initially had a tendency to rise, in accordance with simulated plasma concentration curves. DHE trough levels were about 0.5 ng/ml and were well above the assumed minimum effective value to induce venoconstriction (0.06 ng/ml). Dextran concentrations were significantly higher when DHE was co-administered, possibly, due to changes in plasma volume. It is concluded that DHE 0.5 mg s.c. twice daily will give an adequate plasma concentration and that there was no important interaction between it and infused dextran 70.