Pharmacokinetics of ergotamine in healthy volunteers following oral and rectal dosing

Abstract

Twenty-four healthy volunteers participated in a study on the disposition of ergotamine following oral and rectal administration. Plasma samples were collected surrounding each dose of medication and a new mass spectrometry method was used for quantitation of the samples. A mean peak plasma concentration of 454 pg/ml was measured an average of 50 min following a 2 mg rectal dose. In contrast, the 2 mg oral dose produced a mean peak plasma concentration of 21 pg/ml an average of 69 min following the dose. Area under the concentration time curve indicated a relative bioavailability of 5% for the oral dosage form. Conflicting data on ergotamine disposition highlight the factors which may be responsible for determining bioavailability and pharmacologic activities of the compound.

Ergotamine and Dihydroergotamine: History, Pharmacology, and Efficacy

“…A second peak plasma concentration has been observed in some studies after about 48 hours, which suggests enterohepatic recirculation 26 . Elimination of E follows a biphasic pattern, with mean half‐lives of approximately 10 minutes and 3.4 hours 31 …”

“…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 31 .…”

Evaluation and Emergency Treatment of Headache

“…69 The oral absorption of ergotamine is erratic, which has extremely important clinical implications. Ergotamine given by suppository to normal volunteers produced blood levels 20-to 30-fold higher than those with the same dose given orally.…”

Office management of benign headache

“…Note that the bioavailability of these agents varies dramatically with route of administration: Ergotamine given by suppository to normal volunteers produces blood levels 20 to 30 times higher than those produced by oral administration of the same dose. 18 Because of these high levels with suppository administration and because oral absorption of a quarter of a suppository and, if no nausea develops, to adjust the dose upward to one third and then one half of a suppository and finally to a full suppository.…”