PHARMACOKINETICS OF DIHYDROERGOTAMINE IN HEALTHY-VOLUNTEERS AND IN NEUROLOGICAL PATIENTS AFTER A SINGLE INTRAVENOUS-INJECTION

Abstract

The pharmacokinetics of dihydroergotamine (DHE) was studied in healthy volunteers (n = 6) and in neurological patients (n = 12). After a single 1.0 mg i.v. injection (n = 5) DHE quickly disappeared (T1/2 [half life] = 1.07 min) from the serum, and no cumulative properties were found (T1/2.beta. [elimination phase half life] = 32.9 min, Vdss [volume of distribution at steady state] = 0.33 1/kg, Cltot [total serum clearance] = 1055.7 ml/min). In saliva (dose 1.0 mg, n = 6) and CSF (dose 0.5 mg, n = 12) there were no measureable amounts of DHE after a single i.v. dose. The 32 h cumulative urinary excretion was 0.02-0.04% of the 1.0 mg i.v. dose. In 1 subject renal (0.18 ml/min) and extrarenal (692.9 ml/min) clearance of DHE was calculated. DHE is probably eliminated mainly by hepatic metabolism. The pharmacokinetic properties of DHE indicate a fast clinical response without a cumulative action.