sumatriptan, Imitrex
Cost-effectiveness of sumatriptan in a managed care population.

Legg RF, Sclar DA, Nemec NL, Tarnai J, Mackowiak JI.

College of Pharmacy, Washington State University, Pullman, USA.

We conducted an open-labeled study to determine whether sumatriptan is more cost-effective than other therapies used to treat migraine headache. We contacted by phone 220 sumatriptan users enrolled in QualMed, a health maintenance organization (HMO) in Spokane, Washington. Of these, 203 met the inclusion criteria and 164 (81%) completed our telephone survey. The main outcome measures were healthcare costs to the HMO and number of days free of migraine-related disability before and after sumatriptan treatment. Before sumatriptan treatment, 89% of patients reported severe migraine, compared with 63% after sumatriptan treatment. The number of monthly migraine disability days decreased from 6.5 days per month before sumatriptan to 3.9 days per month after sumatriptan. Healthcare utilization rates (ie, number of hospitalizations, emergency department visits) and costs were lower after the patients began taking sumatriptan. The number of different over-the-counter medicines and prescription medications (other than sumatriptan) taken for migraine disabilities decreased. Although total drug expenditures per month increased, the total migraine healthcare expenditure was 41% lower after sumatriptan was initiated. The cost-effectiveness ratio was 47% more favorable after patients started taking sumatriptan. Overall, patients reported fewer migraine-related disabilities, had lower migraine severity scores, and used fewer healthcare resources when taking sumatriptan. These changes resulted in a better cost-effectiveness ratio for migraine treatment.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10169243&dopt=Abstract sumatriptan Imitrex



sumatriptan, Imitrex
Economic evaluation of oral sumatriptan compared with oral caffeine/ergotamine for migraine.

Evans KW, Boan JA, Evans JL, Shuaib A.

Saskatchewan Health, Regina, Canada. twws iname.com

We conducted an economic comparison of oral sumatriptan with oral caffeine/ergotamine in the treatment of patients with migraine. Cost-effectiveness, cost-utility and cost-benefit analyses were conducted from societal and health-departmental perspectives. A decision tree was used. Utilities were assigned to health states using the Quality of Well-Being Scale. Simple and probabilistic sensitivity analyses were also carried out. From a societal perspective, using sumatriptan instead of caffeine/ergotamine resulted in an incremental cost-effectiveness ratio of -25 Canadian dollars ($Can) per attack aborted, an incremental cost-utility ratio of -$Can7507 per quality-adjusted life-year (QALY), and a net economic benefit of $Can42 per patient per year (1995 values). From the perspective of the health department, the incremental cost-effectiveness ratio was $Can98 per attack aborted, the incremental cost-utility ratio was $Can29,366 per QALY; the grade of recommendation based on past decisions regarding health technology for adoption into health insurance plans was 'moderate'. Sensitivity analysis showed that the results were robust to relatively large changes in the input variables. The incremental health benefits obtained from using oral sumatriptan rather than oral caffeine/ergotamine were achieved at moderately acceptable incremental costs, if past decisions on the adoption of other health technologies are used as a guide.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10174323&dopt=Abstract sumatriptan Imitrex



sumatriptan, Imitrex
5-HT1-like and 5-HT2A receptors mediate 5-hydroxytryptamine-induced contraction of rabbit isolated mesenteric artery.

Yildiz O, Tuncer M.

Department of Pharmacology, Faculty of Medicine, Gulhane Military Medical Academy, Ankara, Turkey.

The contractions induced by 5-hydroxytryptamine (5-HT) and the 5-HT1-like receptor agonist, sumatriptan, were investigated in the open ring preparations of rabbit mesenteric artery in order to characterize the 5-HT receptors. 5-HT induced concentration-dependent contractions. Sumatriptan did not induce any contraction of unstimulated rings, whereas it elicited concentration-dependent contractions in preparations given a moderate tone by a threshold concentration of prostaglandin F2 alpha (PGF2 alpha). Pargyline, cocaine or normetanephrine were without significant effect on the contractions induced by 5-HT and sumatripan. The 5-HT concentration-effect curve was clearly biphasic. Methiothepin (0.01 microM) shifted the both phases of the concentration-effect curve to the right. Ketanserin (0.1 microM) shifted the second, low affinity, phase and prazosin did not alter concentration-effect curve to 5-HT. The sumatriptan concentration-effect curve was shifted by methiothepin (0.01 microM) to the right (pKB = 9.19) but not by ketanserin (1 microM). Concentration-effect curves to 5-HT and sumatriptan were not affected by the 5-HT3 receptor antagonist tropisetron (1 microM). These results suggest that 5-HT1-like type receptors are responsible for the first phase of 5-HT-induced contraction and 5-HT2A receptor for the second phase, in rabbit mesenteric artery. Sumatriptan-induced contractions appear to be mediated by 5-HT1-like type receptors in this artery. These results also suggest that this kind of amplification may be a common feature of vascular 5-HT1-like type receptor as has been shown in other vascular segments such as rabbit femoral, iliac and renal arteries, and guinea-pig iliac artery.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7477434&dopt=Abstract sumatriptan Imitrex



sumatriptan, Imitrex
Cerebral blood flow effects of sumatriptan in drug combinations in the baboon model.

Dormehl IC, Oliver DW, Hugo N.

Atomic Energy Corporation Institute for Life Science, University of Pretoria, Republic of South Africa.

Sumatriptan (CAS 103628-46-2, Imigran) has established itself as an important therapeutic agent in the treatment of migraine. Although considerable understanding of, in particular, the vascular pathophysiology of migraine has been gained during the past decade, the pathophysiology and mediators involved in the pain experience during migraine ar during migraine are not yet fully explained. The mechanisms behind the pharmacological effects of sumatriptan are still only partially understood. In the present study the effects of sumatriptan on drug induced cerebral blood flow increases in the baboon model were investigated using 99mTc-HMPAO (hexamethylpropylene amine oxime) and SPECT (single photon emission computed tomography). Sumatriptan selectively reduced drug induced cerebral blood flow increases. The effects of halothane anaesthesia and acetazolamide on cerebral blood flow were not reversed by sumatriptan, while the effect of nimodipine was attenuated by 47% (to the level of cerebral blood flow below the normal flow baseline). These results support multiple mechanisms for sumatriptan involving vascular neurotransmission and neurogenic inflammatory responses via serotonin receptor stimulation and Ca2+ mobilization. Drug-drug interactions are further implicated through this study.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7488311&dopt=Abstract sumatriptan Imitrex



sumatriptan, Imitrex
[Subcutaneous sumatriptan in the treatment of migraine attacks. An analysis of its long term efficaciousness and tolerance]

[Article in Spanish]

Leira R, Suarez C, Castillo J, Lema M, Noya M.

Servicio de Neurologia, Hospital General de Galicia Clinico Universitario, Santiago de Compostela.

We present the results of treatment with subcutaneous sumatriptan in migraine attacks. The study comprised forty-two patients suffering from migraine both with and without aura, with migraine attacks not susceptible to analgesics, non-steroid anti-inflammatory drugs (NSAID), ergotics or else intolerance to the same. Two groups were independently analyzed, one consisting of ten patients who had menstrual migraine continually for twelve months, the other consisting of thirty-two patients suffering from migraine with and without aura for six months. We assessed the effectiveness of the drug (reduction in the intensity and duration of the attack, action, speed, recurrence) and tolerance (adverse effects). The effectiveness of sumatriptan in relieving headache was 75.9% (80% in the case of the menstrual migraine group and 71.8% in the case of the migraine with and without aura group). This effectiveness was maintained in a similar fashion by analyzing independently the first and last months of treatment. Adverse effects were noted in 38.7% of patients treated (40% for the menstrual migraine group, 37.5% for those with migraine with and without aura). The most frequent effects were pain at the point of injection, a feeling of general tiredness, nausea and a sensation of tension in the neck or chest. These effects were largely slight and short lived. No serious adverse effects were reported. A long term analysis carried out on the menstrual migraine group shows the efficacy of sumatriptan is kept up, with improved tolerance of the drug and a decrease in the number of negative side effects noted.(ABSTRACT TRUNCATED AT 250 WORDS)

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7497233&dopt=Abstract sumatriptan Imitrex



sumatriptan, Imitrex
Differences in the effects of ketanserin and GR127935 on 5-HT-receptor mediated responses in rabbit saphenous vein and guinea-pig jugular vein.

Razzaque Z, Longmore J, Hill RG.

Merck Sharp and Dohme Research Laboratories, Neuroscience Research Centre, Harlow, Essex, UK.

Ketanserin has higher affinity for 5-HT1D alpha receptors compared to 5-HT1D beta receptors, whereas, GR127935 (N-[4-methoxy-3-(4-methyl-1-piperazinyl)phenyl]-2(methyl-4(-(5-methyl- 1,2,4-oxadiazol-3-yl)[1,1-biphenyl]-4-carboxamide), a novel and selective 5-HT1D receptor antagonist, has higher affinity for 5-HT1D beta receptors compared to 5-HT1D alpha receptors. In the present study, we compared the effects of ketanserin and GR127935 on sumatriptan-induced responses of rabbit saphenous vein and guinea-pig jugular vein. In rabbit saphenous vein, contractile responses elicited by sumatriptan were antagonised by ketanserin (pA2 = 6.76) and GR127935 (apparent pA2 = 9.4). In guinea-pig jugular vein, concentration-dependent relaxations evoked by sumatriptan were antagonised by ketanserin and GR127935 (apparent pA2 = 5.9 and 10, respectively). Ketanserin but not GR127935, inhibited Ca(2+)-induced contraction of depolarised strips of guinea-pig ileum longitudinal muscle/myenteric plexus, however, in rabbit saphenous vein and guinea-pig jugular vein, 5-HT receptor mediated responses were insensitive to nifedipine (Ca2+ channel blocker), eliminating the possibility that the inhibitory effects of ketanserin and GR127935 were due to the blockade of voltage-operated Ca2+ channels. Thus, antagonism by ketanserin and GR127935 confirms the presence of 5-HT1D receptors in rabbit saphenous vein and guinea-pig jugular vein. The differential effects of ketanserin and GR127935 on responses elicited by sumatriptan in rabbit saphenous vein and guinea-pig jugular vein may reflect either species differences in 5-HT1D receptors or the involvement of 5-HT1D alpha and 5-HT1D beta receptor subtypes.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7498311&dopt=Abstract sumatriptan Imitrex



sumatriptan, Imitrex
Assessment of peripheral vascular effects of antimigraine drugs in humans.

van Es NM, Bruning TA, Camps J, Chang PC, Blauw GJ, Ferrari MD, Saxena PR, van Zwieten PA.

Department of Nephrolog, University Hospital Leiden, The Netherlands.

The vascular beds of the forearm and finger can be used to study the peripheral effects of antimigraine drugs under normal and pathologic circumstances. We have investigated the novel antimigraine drug sumatriptan, a selective agonist for 5HT1 receptors. Its antimigraine effect may be attributed, at least in part, to constriction of cranial arteriovenous anastomoses (AVAs). In assessing the peripheral vascular effects of sumatriptan we used a forearm and finger blood flow model. Forearm blood flow (FBF) is mainly determined by resistance vessels, whereas finger blood flow (FiBF) mainly involves skin vessels, which contain many AVAs. Changes in FBF and FiBF can be assessed using venous occlusion plethysmography. Changes in AVA flow are determined by measuring the patency of the vascular beds of the forearm and hand to well-defined radiolabelled microspheres, which are injected into the brachial artery. We report the effects of sumatriptan on FBF, FiBF and AVA flow when administered into the brachial artery of healthy volunteers, and discuss the peripheral vascular effects of therapeutic doses of sumatriptan when given subcutaneously in migraine patients during and between attacks.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7585925&dopt=Abstract sumatriptan Imitrex