The Clinical Pharmacology, Pharmacokinetics and Metabolism of Sumatriptan

Abstract

Clinical pharmacology studies were undertaken in young healthy volunteers, in a small number of elderly subjects and in migraine subjects during and between attacks. Absorption after subcutaneous and oral administration was rapid. Bioavailability was nearly 100% after subcutaneous administration and averaged 14% after oral administration. Elimination was predominantly by metabolism to a non-active indoleacetic acid analogue. The plasma half-lives of sumatriptan and the metabolite were about 2 h. Pharmacokinetic and pharmacodynamic variables were similar in all groups studied and were not altered by the presence of food, alcohol, dihydroergotamine or prophylactic migraine treatments. Sumatriptan produced a number of minor adverse events, but had no clinically significant effect on routine haematological or biochemical investigations using the intravenous, subcutaneous or oral routes. Transient rises in blood pressure were observed which were no greater than those that would be anticipated during moderate exercise. The physician-administered subcutaneous injection resulted in transient stinging at the site of injection in many subjects; administration using the auto-injector was better tolerated.

The effects of oral sumatriptan, a 5‐HT1 receptor agonist, on circulating ACTH and cortisol concentrations in man.

“…Functional activity has been demonstrated at the 5-HTID but not at the 5-HTlA subtype [30]. Similarity between time-profiles for the observed change in circulating ACTH and cortisol concentrations and the plasma concentration of sumatriptan following an oral dose [31], strongly suggests a direct relationship with the plasma concentration of sumatriptan. Sumatriptan would appear to modulate the release of ACTH from the pituitary which, in turn, modulates the release of cortisol from the adrenal cortex.…”

Formulation and Optimization of Orally Disintegrating Tablets of Sumatriptan Succinate

“…[31][32][33][34] The possible reason for the appearance of double peaks in many rabbits could be to the presence of two compartment absorption phases with only one disposition phase. 35,36) The probable reasons for multiple peaks may be due to alteration in the gastric motility by sumatriptan 37,38) and/or presence of multiple absorption sites for sumatriptan in the gastrointestinal tract of rabbits.…”

Use of High Sumatriptan Dosages During Episodic Cluster Headache: Three Clinical Cases

“…In fact, it seems to inhibit the release of calcitonin gene-related peptide. [1][2][3][4][5][6] The high selectivity of this molecule explains the fact that it does not alter flow resistance of the coronary and peripheral vessels 7 unlike, for example, ergotamine. [8][9] At present, sumatriptan is available in Italy as 100-mg tablets and as preloaded syringes containing 6 mg for subcutaneous administration by an autoinjector device.…”