Interspecies similarities in the disposition of 3H-dihydroergotamine following subcutaneous administration in man and rabbits.

ABSTRACT

The disposition of dihydroergotamine methanesulfonate following single subcutaneous doses was studied in man and the rabbit using radiotracer techniques. 3H-Dihydroergotamine was almost immediately and completely absorbed from the injection site; peak blood radioactivity levels were attained within 1 h of drug administration in both species. The disappearance of radioactivity from blood was biphasic, with t 1/2,alpha and t 1/2,beta values of 2.9 and 16.9 h, respectively, in man and 2.9 and 14.7 h, respectively, in the rabbit. Apparent volumes of distribution were 18.9 Liter/kg in man and 30.4 Liter/kg in the rabbit. The excretion pattern of dihydroergotamine and its metabolites was also similar for the two species, with biliary elimination being the predominant route. At 4-5 days postdosing, 80-85% of the administered radioactivity was recovered in the feces and urine. The rabbit appears to be an adequate animal model for the study of dihydroergotamine pharmacokinetics in man.