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

Abstract

1 Fifteen migraine patients were administered 2 mg ergotamine tartrate in a partial cross-over design as a single, oral tablet, rectal suppository and rectal solution. Eight of these patients were in a previous investigation given 0.5 mg ergotamine tartrate intravenously. The blood samples were taken up to 54 h after oral and suppository while it was followed for only 3 h after rectal solution. The chemical analysis was performed by applying h.p.l.c. method with a limit of sensitivity of 0.1 ng/ml ergotamine base in plasma.2 No ergotamine was detected in the blood samples after the oral route, whereas small and very variable quantities was found in blood after the rectal route. Regular calculation of bioavailability could therefore not be performed. An estimate of the maximal possible bioavailability was found to yield a mean value of 2% (tablets); 5% (suppositories) and 6% (rectal solution). Rectal solution elicited faster absorption and the extent of absorption was significantly higher (P < 0.05) than for the suppository.

Triptans vs Other Drugs for Acute Migraine. Are There Differences in Efficacy? A Comment

“…The oral triptans are superior to oral ergotamine which has a very low oral bioavailability 17‐19 . By the rectal route and by injection, the ergot alkaloids, ergotamine and DHE, seem to be equipotent to triptans as would be expected because both classes of drugs are acting on the same 5‐HT 1B/1D receptor 20 .…”

“…Oral ergotamine plus caffeine was found inferior to oral sumatriptan, rizatriptan, eletriptan, and almotriptan (Table 1). 3,13‐16 Because of an extremely low bioavailability (<1%), the oral route of administration is not optimal for this drug 12,17‐19 . In contrast, rectal ergotamine has a bioavailability of 1‐3% 20 .…”

Ergotamine and Dihydroergotamine: History, Pharmacology, and Efficacy

“…Ergotamine and DHE have low bioavailability and are subject to substantial (greater than 90%) first-pass metabolism by the liver following oral administration; as a result very little of the unchanged parent drug reaches the systemic circulation. [23][24][25][26] However, several of the metabolites of E and DHE have biologic activity similar to that of the parent drug and are often present in concentrations several times higher than that of the parent compound. 27,28 Ergotamine and DHE are strongly sequestered by tissues, which could contribute to the persistence of biologic effects well after the parent drug or metabolites can no longer be detected in plasma.…”

“…1 Ergotamine tartrate is rapidly but incompletely and variably absorbed after oral (approximately 1%), rectal (1% to 2%), or IM (47%) administration. 23,24,30 Peak plasma levels are attained approximately 1 hour after oral or rectal administration. 23,31 Plasma levels are highest following rectal administration.…”

Dihydroergotamine, Ergotamine, Methysergide and Sumatriptan – Basic Science in Relation to Migraine Treatment

“…bioavailability (100%), oral bioavailability of ergotamine is <1%, rectal bioavailability of ergotamine is 1–3%, and i.m. bioavailability of ergotamine is 47% 56,57 . Ergotamine is metabolized in the liver by largely undefined pathways, and 90% of the metabolites are excreted in the low oral bioavailability (less than 1%) because of incomplete drug passage across the gastrointestinal mucosa and a high first‐pass metabolism 57,58 .…”