Human Plasma Levels of Some Anti‐migraine Drugs

Abstract

SYNOPSIS Four compounds of therapeutic value in the treatment of migraine attacks or for the prophylaxis of migraine and other vascular headaches, ergotamine, dihydroergotamine, methysergide and pizotifen are given in low dosages and achieve low in vivo concentration. Human plasma levels were determined by measurement of radioactivity after oral administration of the corresponding radioactively labeled compounds. The labeling of the four compounds with tritium or carbon‐14 is briefly described. The procedure to measure radioactivity of the blood samples is given. The values from single dose experiments in healthy volunteers were analysed based on a compartment model which allows for the formation of metabolites. The calculated pharmacokinetic constants have been used for simulations and predictions of plasma levels after different therapeutic dosages.

Low bioavailability of ergotamine tartrate after oral and rectal administration in migraine sufferers.

“…In previous studies (Aellig & Nuesch, 1977;Meier & Schreier, 1976) with tritium-labelled ergotamine peak plasma concentrations of ergotamine from 1.5 to 3 ng/ml after administration of 1 and 4 mg ergotamine tartrate orally was found. Our results with ergotamine tablets strongly indicate that what was measured in these studies was mostly metabolites.…”

Fate and disposition of bromocriptine in animals and man. I: Structure elucidation of the metabolites

“…(Table I) were isolated from rat bile. Metabolites 1 and 3 (2-bromo-lysergic acid amides) : Metabolites I and 3 were 2-bromo-Iysergic acid amide (3) and 2-bromo-isolysergic add amide (1). Their identity with the authentic reference compounds was proved by comparative TLC and HPLC.…”

“…[6-methyl-14C]Bromocriptine was prepared according to the procedure described for [ 14C]methysergide (3). The carbon-14 label was introduced by alkylating the 6-desmethyl derivative of bromocriptine with [14C]methyl iodide in acetonitrile in the presence of ethyldiisopropylamine (4).…”

Ciclazindol and mazindol on glucose uptake into human isolated skeletal muscle: no interaction of mazindol with methysergide.

“…The effect of mazindol is not influenced by the addition of methysergide in concentrations corresponding to, and in excess of, those probably reached in the plasma after therapeutic doses, namely 8.5-60 ng/ml (Meier & Shreier, 1976). …”