sumatriptan, Imitrex
off absorption, pharmacodynamics, metabolism and excretion of 14C-sumatriptan following intranasal administration to the beagle dog.

Barrow A, Dixon CM, Saynor DA, Perren MJ, Stowe R, Smith I.

Bioanalysis and Drug Metabolism Division, GlaxoWellcome Research and Development, Ware, Herts, U.K.

The pharmacodynamics, pharmacokinetics, metabolism, and excretion of 14C-sumatriptan have been studied in the beagle dog following administration by the intranasal and other routes. The pharmacological response which was monitored, an increase in carotid arterial vascular resistance, correlated with the plasma levels of unchanged sumatriptan following intranasal, intravenous, or intraduodenal administration to the anaesthetised dog. The pharmacokinetics and metabolism of sumatriptan were then confirmed in conscious male and female dogs. Intranasal administration of 14C-sumatriptan resulted in rapid absorption of part of the dose. The overall bioavailability of sumatriptan was 40-50%. Sumatriptan was eliminated from plasma with a half-life of 1.5 or 1.9 h after intravenous or intranasal dosage respectively. Radioactivity was largely excreted in urine (up to 75% of the dose) with small amounts in the bile and faeces after intravenous and intranasal dosing, as sumatriptan and a major metabolite. The results from these studies suggest that intranasal administration provides a viable method for delivering sumatriptan to the systemic circulation.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9210982&dopt=Abstract sumatriptan Imitrex



sumatriptan, Imitrex
Differential distribution of [3H]sumatriptan binding sites (5-HT1B, 5-HT1D and 5-HT1F receptors) in human brain: focus on brainstem and spinal cord.

Castro ME, Pascual J, Romon T, del Arco C, del Olmo E, Pazos A.

Department of Physiology and Pharmacology, University of Cantabria, Santander, Spain.

We report on the autoradiographic distribution of 5-HT1B, 5-HT1D and 5-HT1F receptor subtypes in human brain, focusing on the brainstem and cervical spinal cord. We have used [3H]sumatriptan as a radioligand in the presence of suitable concentrations of 5-CT (5-carboxamidotryptamine) to define 5-HT1F receptors, and ketanserin, to discriminate between 5-HT1B and 5-HT1D receptors. In the brainstem the highest concentrations of [3H]sumatriptan binding sites were seen in substantia nigra. The spinal trigeminal nucleus, substantia gelatinosa of the spinal cord, nucleus of the tractus solitarius and periaqueductal grey, also showed significant levels of [3H]sumatriptan binding sites. In the brainstem and spinal cord the total population of 5-CT-insensitive receptors, corresponding to 5-HT1F receptors, ranged from 9.8% in the periaqueductal grey to 53.4% in the substantia gelatinosa. This population represented 67.0% of binding in layer V of the frontal cortex. The decrease in [3H]sumatriptan binding in the presence of 200 nM ketanserin, indicative of the presence of 5-HT1D receptors, was very limited throughout the human brain, only reaching 20% of total specific binding over the periaqueductal grey. The proportion of [3H]sumatriptan binding sites displaced by 5-CT and insensitive to ketanserin, corresponding to 5-HT1B receptors, was, in general, the most abundant, ranging from 43.8% in substantia gelatinosa to 69.9% in the periaqueductal grey. Significant levels of 5-HT1B and 5-HT1D receptors found in migraine control pain areas suggest their involvement in antinociceptive mechanisms.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9225278&dopt=Abstract sumatriptan Imitrex



sumatriptan, Imitrex
Stability of sumatriptan succinate in extemporaneously prepared oral liquids.

Fish DN, Beall HD, Goodwin SD, Fox JL.

Department of Pharmacy Practice, University of Colorado Health Sciences Center, Denver 80262, USA. doug.fish uchsc.edu

The stability of sumatriptan succinate in extemporaneously prepared oral liquids was studied. Suspensions of sumatriptan (as the succinate salt) in Ora-Sweet, Ora-Sweet SF, and Syrpalta syrups (Paddock Laboratories and Humco Laboratory) were extemporaneously compounded to produce a sumatriptan concentration of 5 mg/mL. Each suspension was prepared in triplicate. The suspensions were stored at 4 degrees C in amber glass bottles for 60 days. Two 1-mL samples were removed from each bottle initially and on days 2, 7, 14, 21, 28, 35, and 60. Sumatriptan concentrations were determined by high-performance liquid chromatography. The samples also underwent visual inspection and microbial testing. The mean concentration of sumatriptan in all suspensions remained above 90% of the initial concentration for up to 21 days. By day 28, the sumatriptan concentration of all suspensions had decreased to less than 90% of the initial concentration. None of the suspensions had microbial growth up to day 28, and there were no visible changes in the suspensions throughout the study period. Sumatriptan 5 mg/mL (as the succinate salt) in three oral suspensions was stable for up to 21 days when stored without light at 4 degrees C.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9248606&dopt=Abstract sumatriptan Imitrex



sumatriptan, Imitrex
Cost benefit of sumatriptan to an employer.

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

Center for Health Services Research & Policy, Qual-Med Health Plan of Washington, Inc., Inland Northwest Division, Spokane, Wash, USA.

Benefit and occupational health managers need information on whether new treatments, such as sumatriptan, for migraine headache improve organizational or individual performance. A work productivity outcomes assessment was conducted among sumatriptan-using employees of an Independent Practice Association-health maintenance organization population. Of the 164 sumatriptan users, 101 full-time employees were surveyed by telephone once in an open-label, before-after design. The results revealed that lost labor costs, a function of days missed from work and reduced productivity at work as a result of migraine, were decreased after sumatriptan treatment initiation. Incremental benefit of this reduction in lost productivity is valued at $435/month per employee. The sumatriptan cost associated with this benefit is $43.78/month. The benefit-to-cost ratio is 10:1. Other costs and benefits were excluded. In conclusion, the availability of sumatriptan for migraine headache treatments in this IPA-HMO resulted in improved work productivity and had a net benefit for the employer.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9253726&dopt=Abstract sumatriptan Imitrex



sumatriptan, Imitrex
Serotonergic effects and extracellular brain levels of eletriptan, zolmitriptan and sumatriptan in rat brain.

Johnson DE, Rollema H, Schmidt AW, McHarg AD.

Department of Neuroscience, Pfizer Global Research and Development, MS 8220-4159, Groton, CT 06340, USA.

In vivo microdialysis was used to assess the central serotonergic effects and extracellular brain levels of the 5-HT(1B/1D) receptor agonists eletriptan, zolmitriptan and sumatriptan in rats after intravenous and intracerebral administration, while their binding affinities and functional potencies were determined at 5-HT(1B), 5-HT(1D) and 5-HT(1A) receptors. In vitro studies showed that all three triptans are high affinity, full agonists at 5-HT(1B/1D) receptors, but that sumatriptan is functionally less potent as a 5-HT(1B/1D) agonist than zolmitriptan and eletriptan. Local intracortical perfusion with the compounds via the dialysis probe decreased cortical 5-HT (5-hydroxytryptamine, serotonin) release with ED(50) values of approximately 0.1 microM for eletriptan and zolmitriptan and 0.5 microM for sumatriptan. At 3.2 mg/kg i.v., both eletriptan and zolmitriptan decreased 5-HT levels by about 35%, while sumatriptan had no effect, despite the fact that maximal sumatriptan concentrations in cortical dialysates were higher (8.8 nM at 20 min) than those of zolmitriptan (5.9 nM at 20 min) and eletriptan (2.6 nM at 40 min). The observation that eletriptan and zolmitriptan produce almost identical central serotonergic effects, after intracerebral as well as after systemic administration, is in agreement with their comparable functional 5-HT(1B/1D) receptor agonist potencies and their free levels in cortical dialysates after 3.2 mg/kg i.v. On the other hand, the lack of central serotonergic effects of 3.2 mg/kg i.v. sumatriptan is likely due to its weaker functional 5-HT(1B/1D) receptor agonist potency than eletriptan and zolmitriptan, rather than lower brain levels, consistent with sumatriptan's fivefold lower potency after intracerebral administration.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11513839&dopt=Abstract sumatriptan Imitrex



sumatriptan, Imitrex
Impact of chest pain on cost of migraine treatment with almotriptan and sumatriptan.

Wang JT, Barr CE, Goldfarb SD.

Pharmacia Corporation, Peapack, NJ.

Chest-related symptoms occur with all triptans; up to 41% of patients with migraine who receive sumatriptan experience chest symptoms, and 10% of patients discontinue treatment. Thus, the cost of chest pain-related care was estimated in migraineurs receiving almotriptan 12.5 mg versus sumatriptan 50 mg. A population-based, retrospective cohort study used data to quantify the incidence and costs of chest pain-related diagnoses and procedures. An economic model was constructed to estimate annual cost savings per 1000 patients receiving almotriptan versus sumatriptan based on the reported rates of chest pain. Annual direct medical cost avoided was calculated for a hypothetical health plan covering 1 million lives. Among a cohort of 1390 patients, the incidence of chest pain-related diagnoses increased significantly by 43.6% with sumatriptan (P=.003). Aggregate costs for chest pain-related diagnoses and procedures increased from $22 713 to $30 234. Payments for inpatient hospital services, costs for primary care visits, and costs for outpatient hospital visits increased by over 100%, 53.1%, and 14.4%, respectively. The model predicted $11 215 in direct medical cost savings annually per 1000 patients treated with almotriptan versus sumatriptan. Annual direct medical costs avoided totaled $194 358, and when applied to recent estimates of 86 million lives currently covered by almotriptan treatment, translates into an annual cost savings of just under $17 million for chest pain and associated care. Thus, using almotriptan in place of sumatriptan will likely reduce the cost of chest pain-related care.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11966863&dopt=Abstract sumatriptan Imitrex



sumatriptan, Imitrex
Comparison of the cardiovascular effects of the novel 5-HT(1B/1D) receptor agonist, SB 209509 (VML251), and sumatriptan in dogs.

Parsons AA, Parker SG, Raval P, Campbell CA, Lewis VA, Griffiths R, Hunter AJ, Hamilton TC, King FD.

Department of Neurology Research, SmithKline Beecham Pharmaceuticals, Harlow, Essex, England.

The systemic cardiovascular effects of a novel 5-hydroxtryptamine (5-HT)(1B/1D)-receptor agonist were investigated in the anaesthetised dog. SB 209509 (VML 251) was more potent than sumatriptan in producing increases in carotid vascular resistance after intravenous administration and was similar in potency to sumatriptan after sequential intraduodenal administration at 30-min intervals. In open-chest dogs, sequential intravenous administration of SB 209509 or sumatriptan produced marked increases in carotid vascular resistance without changing coronary vascular resistance. In contrast to sumatriptan, after administration of high doses of SB 209509 (>790 nmol/kg), a reduction in coronary vascular resistance was observed. After a single bolus intraduodenal dose of SB 209509 (260, 520, or 790 nmol/kg), increases in carotid vascular resistance could be detected over a 5-h period. Sumatriptan (i.d.), 2.4 micromol/kg but not 700 nmol/kg, produced a sustained effect similar to the effects of SB 209509 (790 nmol/kg). In all experiments, SB 209509 and sumatriptan had minimal effects on arterial blood pressure or heart rate but produced marked changes in carotid vascular resistance over the same concentration range. SB 209509 was rapidly absorbed after intraduodenal administration in conscious dogs and had good bioavailability. These data indicate that SB 209509 is a potent 5-HT(1B/1D)-receptor agonist that is rapidly absorbed from the duodenum. The effects of SB 209509 are long lasting and selective for the carotid vascular bed.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9268233&dopt=Abstract sumatriptan Imitrex