Disease relevance of Avitriptan

• Patients (n = 51) who had no clinically significant abnormality at baseline received a high dose (150 mg) of avitriptan orally outside of a migraine attack [1].
• Only those hypertensive patients receiving medication for hypertension should receive anti-migraine medications, such as avitriptan, which are 5HT1-like receptor agonists [2].

High impact information on Avitriptan

• There were no changes in the pharmacokinetics of avitriptan after coadministration with propranolol [3].
• We investigate whether symptoms of pressure, tightness, and/or pain in the chest, neck, and/or throat after administration of the 5HT1B/1D agonist avitriptan were associated with objective impairment of the myocardial function on 12-lead electrocardiogram (ECG), continuous ECG (Holter) monitoring, and echocardiography [1].
• Overall, avitriptan has consistent, linear pharmacokinetics and increases systolic and diastolic blood pressure in a predictable manner at a higher plasma concentration [4].
• The change in pulse rate and supine systolic and diastolic blood pressure was determined as pharmacodynamic effects of avitriptan [4].
• The study was conducted to characterize the pharmacokinetics, absolute bioavailability, and disposition of avitriptan after intravenous (iv) and oral administrations of [14C]avitriptan in rats and oral administration of [14C]avitriptan in humans [5].

Biological context of Avitriptan

• The intra- and inter-subject variability (%CV) in the Cmax and AUC of avitriptan in the fasted and fed conditions ranged from 10 to 60% in male and female subjects [6].
• It was also apparent that avitriptan exerted a secondary pharmacologic effect that temporarily suspended gastric emptying in the fasted treatment [7].
• There were no gender differences nor a gender by food interaction in the pharmacokinetics of avitriptan [6].
• Thus, it appears that avitriptan absorption and bioavailability are highly sensitive to presence of food in the stomach and any food-related changes in gastric emptying time and gastrointestinal motility [8].

Anatomical context of Avitriptan

• In this study we sought to compare the effects of CP122,288 and avitriptan on jugular vein CGRP release after stimulation of the superior sagittal sinus (SSS) in the cat [9].
• Scintigraphic analysis also demonstrated that upon emptying from the stomach, avitriptan was rapidly absorbed from the upper small intestine [7].

Associations of Avitriptan with other chemical compounds

• Using these two models, we have now investigated the effects of avitriptan (BMS-180048; 3-[3-[4-(5-methoxy-4-pyrimidinyl)-l-piperazinyl[propyl]-N-methyl-l H-indole-5-methane-sulfonamide monofumarate), a new 5-HT 1B/1D receptor agonist [10].
• Elevation in gastric pH caused by food was not found to be responsible for the food-related decrease in bioavailability of avitriptan since ranitidine pretreatment did not lead to a decrease in bioavailability [8].

Analytical, diagnostic and therapeutic context of Avitriptan

• Avitriptan was extensively metabolized after oral administration, with the unchanged drug accounting for 32% and 22% of the total radioactivity in plasma in rats and humans, respectively [5].
• This study demonstrates that the potent inhibitor of PPE, CP122, 288, which has been shown in clinical trials to be ineffective in treating acute migraine attacks, had no effect on CGRP release, whereas the effective anti-migraine drug and relatively impotent inhibitor of PPE, avitriptan, blocked CGRP release [9].
• In vivo evaluation of the absorption and gastrointestinal transit of avitriptan in fed and fasted subjects using gamma scintigraphy [7].
• Serial blood samples were collected over 24 h after dosing and analyzed by a validated HPLC method for avitriptan [6].

References