sumatriptan, Imitrex
Vasoneuronal coupling in migraineurs after subcutaneous sumatriptan: a TCD study.

Baezner H, Steinke W, Daffertshofer M, Hennerici M.

Department of Neurology, University Heidelberg, Klinikum Mannheim, 68135, Mannheim, Germany. hansjoerb.baezner zmf.ma.uni-heidelberg.de

According to the trigeminovascular model of pain in migraine, sterile neurogenic inflammation of dural vessels stimulates nociceptive fibres of the trigeminal nerve. Sumatriptan, a 5-HT1 receptor agonist, blocks this reaction and mediates vasoconstriction of meningeal arteries. However, it is uncertain, whether sumatriptan also has a vasoconstrictive effect on cerebral arteries, which may influence vasoneuronal coupling and induce secondary cerebral blood flow changes. We studied changes of cerebral blood flow velocity (CBFV) and the pulsatility index (PI) in the posterior cerebral artery (PCA) after stimulus activation before, 10 min and 30 min after subcutaneous application of 6 mg sumatriptan, in order to assess potential vasoactive effects on cerebral circulation. CBFV was recorded from both PCAs simultaneously in 27 migraineurs (twenty women, seven men, mean age 29 years), and arterial blood pressure (BP), heart rate (HR) and respiration rate (RR) were monitored. Although the mean diastolic blood pressure rose significantly from 75 mm Hg to 81 mm Hg (P<0.05) and systolic blood pressure and respiration rates remained constant, average CBFV values remained constant. Similarly, the relative increase of CBFV by visual stimulation, which is clearly higher compared to controls in other studies (55.0% before, 52.6% after 10 min, and 52.4% after 30 min), and absolute mean values for CBFV and PI did not change after visual stimulation. These results provide evidence against the hypothesis that sumatriptan produces vasoconstriction in the intracranial human arterial circulation as a potential risk of cerebral ischemia.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10500262&dopt=Abstract sumatriptan Imitrex



sumatriptan, Imitrex
Cerebral blood flow effects of the nitric oxide donor, nitroglycerin and its drug combinations in the non-human primate model.

Oliver DW, Dormehl IC.

Faculty Pharmacy, Pharmacology, Potchefstroom University for Christian Higher Education, South Africa. fkldwo puknet.puk.ac.za

Nitroglycerin (CAS 55-63-0, Nitrocene) has successfully been used in the management of angina during the last several decades. Although important information on the pharmacological actions and efficacy of nitroglycerin have been extracted, to date, limited research has been conducted on its effects on cerebral blood flow. In recent years, with the aid of SPECT (single photon emission computed tomography) and PET (positron emission tomography) it has been shown that marked cerebral blood flow changes occur under treatment of a wide variet of drugs. Illucidation of the pharmacological mode of action of nitroglycerin has gained momentum with the discovery of nitric oxide (NO) as an endogenous mediator and with the knowledge that nitroglycerin acts as a NO donor. The present study investigated the effects of nitroglycerin (0.25 microgram/kg/min over 10 min) on the cerebral blood flow, using 99mTc-HMPAO (hexamethylpropylene amine oxime) and SPECT, in an anaesthetised primate model, as well as the effects of its drug interactions with therapeutic agents that influence cerebrovascular dynamics, e.g. sumatriptan, nimodipine and acetazolamide. The present study with nitroglycerin indicates that the response time to measure cerebral blood flow effects seems to be present and an important factor as the transient is relatively short. The current treatment regime with nitroglycerin indicates a slight increase, when compared with control control results, although not significant, except for regional significant increases in particular the occipital regions of the brain. Drug interaction between nitroglycerin and nimodipine may occur as a reduction of 20% in cerebral blood flow from the control control was observed in this case. The results for the combination of nitroglycerin with sumatriptan showed a further increase of the cerebral blood flow to near significance, when compared with the control results and is significantly increased (+27%) when compared with sumatriptan treatment alone. Effective treatment with sumatriptan may therefore be compromised with simultaneous administration of nitroglycerin or NO donor drugs. The combination of nitroglycerin and acetazolamide suggested that the increase in cerebral blood flow is primarily attributed to the influence of acetazolamide. The cerebral blood flow effects of these drugs and possible interactions during an angina attack need to be investigated.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10514899&dopt=Abstract sumatriptan Imitrex



sumatriptan, Imitrex
Different approaches to valuing the lost productivity of patients with migraine.

Lofland JH, Locklear JC, Frick KD.

Office of Health Policy and Clinical Outcomes, Thomas Jefferson University, Philadelphia, Pennsylvania 19107-5099, USA. jennifer.lofland mail.tju.edu

OBJECTIVE: To calculate and compare the human capital approach (HCA) and friction cost approach (FCA) methods for estimating the cost of lost productivity of migraineurs after the initiation of sumatriptan from a US societal perspective. DESIGN: Secondary, retrospective analysis to a prospective observational study. SETTING: A mixed-model managed care organisation in western Pennsylvania, USA. PATIENTS: Patients with migraine using sumatriptan therapy. INTERVENTIONS: Patient-reported questionnaires collected at baseline, 3 and 6 months after initiation of sumatriptan therapy. OUTCOME MEASURES: The cost of lost productivity estimated with the HCA and FCA methods. RESULTS: Of the 178 patients who completed the study, 51% were full-time employees, 13% were part-time, 18% were not working and 17% changed work status. Twenty-four percent reported a clerical or administrative position. From the HCA, the estimated total cost of lost productivity for 6 months following the initiation of sumatriptan was $US117905 (1996 values). From the FCA, the six-month estimated total cost of lost productivity ranged from $US28329 to $US117905 (1996 values). CONCLUSIONS: This was the first study to retrospectively estimate lost productivity of patients with migraine using the FCA methodology. Our results demonstrate that depending on the assumptions and illustrations employed, the FCA can yield lost productivity estimates that vary greatly as a percentage of the HCA estimate. Prospective investigations are needed to better determine the components and the nature of the lost productivity for chronic episodic diseases such as migraine headache.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11700778&dopt=Abstract sumatriptan Imitrex



sumatriptan, Imitrex
Human isolated coronary artery contraction to sumatriptan: a post hoc analysis.

Maassen VanDenBrink A, Bax WA, Ramrattan NN, Ferrari MD, Saxena PR.

Department of Pharmacology, Erasmus University Medical Centre, Rotterdam, The Netherlands.

A post hoc analysis was performed on concentration response curves to sumatriptan in 62 human isolated coronary arteries. We determined whether donor-related clinical characteristics (age, sex, cause of death) and properties of the coronary artery (functional endothelial integrity, muscle mass) were related to the potency and efficacy of sumatriptan in contracting the human isolated coronary artery. The efficacy of sumatriptan was inversely related to the functional integrity of the vessel endothelium. Thus, contrary to expectation, coronary artery constriction to sumatriptan seems to be more pronounced in patients with nondiseased coronary arteries where the endothelium is intact. Nevertheless, in view of the high coronary reserve in these patients, myocardial ischemia after the use of sumatriptan is unlikely to occur, whereas in patients with coronary artery disease even a small contraction may be deleterious.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10524658&dopt=Abstract sumatriptan Imitrex



sumatriptan, Imitrex
Cost-effectiveness and cost-benefit of sumatriptan in patients with migraine.

Lofland JH, Kim SS, Batenhorst AS, Johnson NE, Chatterton ML, Cady RK, Kaniecki R, Nash DB.

Office of Health Policy and Clinical Outcomes, Thomas Jefferson University, Philadelphia, PA 19107, USA. jennifer.lofland mail.tju.edu

OBJECTIVE: To investigate the cost-effectiveness and cost-benefit of initiating sumatriptan therapy in patients with acute migraine who were previously taking nontriptan drugs. PATIENTS AND METHODS: This is an economic analysis of a prospective, pretest-posttest, observational 6-month outcomes study of 178 patients with a physician diagnosis of migraine who received their first prescription for sumatriptan between October 1994 and August 1996 and were members of a mixed-model managed care organization in western Pennsylvania. Migraine-related resource use data were obtained from the managed care organization's medical and pharmacy claims databases. The primary outcome measure for this economic analysis was the total disability time that patients experienced because of migraine. Patients reported time missed from work and usual nonwork activities because of migraine on self-administered questionnaires at baseline and at 3 and 6 months after initiation of sumatriptan. RESULTS: Initiation of sumatriptan resulted in a decrease of 662 migraine-disability-days for work and 1236 migraine-disability-days for nonwork activities during the 6 months of the study (decrease from 27.8 to 17.2 days per person), totaling 1898 migraine-disability-days averted with sumatriptan therapy. Migraine-related medical costs were lower after sumatriptan was initiated ($18,351 vs $26,192), whereas migraine-related pharmacy costs were lower with prior nontriptan drug therapy ($22,209 vs $74,861). The overall net cost savings after sumatriptan was initiated in these patients was $222,332 ($1249 per patient) with a benefit-to-cost ratio of $5.67 gained for each health care dollar spent from a societal perspective. The incremental cost-effectiveness ratio was $25 for each additional migraine-disability-day averted by using sumatriptan vs nontriptan drug therapy. Sensitivity analysis showed that changes in medical costs had little effect on the ratios and that sumatriptan remained cost-beneficial across a wide range of patient wages. CONCLUSION: This study showed that initiation of sumatriptan in patients previously receiving nontriptan therapy was cost-effective and had an economic benefit for patients, employers, and society. Sumatriptan also helped patients and physicians achieve goals recommended by the US Headache Consortium by reducing patients' disability and thus improving their ability to function at work and nonwork activities.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11702897&dopt=Abstract sumatriptan Imitrex



sumatriptan, Imitrex
Effects of sumatriptan on nitric oxide and superoxide balance during glyceryl trinitrate infusion in the rat. Implications for antimigraine mechanisms.

Read SJ, Manning P, McNeil CJ, Hunter AJ, Parsons AA.

Neuroscience Research, Smithkline Beecham Pharmaceuticals, New Frontiers Science Park, Third Avenue, Harlow, UK.

Infusion of glyceryl trinitrate (GTN) into patients with migraine precipitates the onset of a migraine attack several hours after completion of the infusion. Using an infusion of GTN into anaesthetised rats, this study investigates the relationship of regional cerebral blood flux rCBF(ldf), cortical nitric oxide (NO) and cortical superoxide concentrations and the effect of sumatriptan on each variable. In saline treated animals, a 30 min infusion of GTN (2 microgram kg(-1) min(-1), i.v.) was found to markedly increase cortical rCBF(ldf) (133+/-3% of baseline) and NO concentrations (141+/-13% of baseline). Superoxide levels exhibited an inverse relationship to NO levels, decreasing below basal to 48+/-14% of baseline. It is hypothesised that high NO levels during GTN infusion may decrease the detectable superoxide due to "leeching" of the superoxide into low level peroxynitrite formation. In the presence of sumatriptan, a decrease below baseline in cortical rCBF(ldf) (82+/-5% of baseline) and NO concentration (64+/-13% of baseline) was observed throughout GTN infusion, although superoxide levels significantly increased above baseline by 105+/-14 nM (p<0.05, ANOVA post hoc LSD test). The mechanism for this action of sumatriptan is unknown but may include; modulation of cell redox state, NO scavenging or direct manipulation of superoxide release.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10564729&dopt=Abstract sumatriptan Imitrex



sumatriptan, Imitrex
HMO direct costs and health care resources use after implementation of a monthly limit on sumatriptan.

Goldfarb SD, Duncan BS, Dans PE, Sloan AS.

Managed Care Pharmacy, Advance Paradigm Clinical Services, Hunt Valley, MD, USA. scott.d.goldfarb am.pnu.com

The health care costs and resource use of patients with migraine before and after a quantity limit on sumatriptan was introduced in an HMO were compared. A longitudinal, retrospective review of a medical claims database and a pharmacy claims database was conducted for two six-month periods before and after a monthly limit (four tablets or injections) on sumatriptan reimbursement was instituted at an independent practice association-model HMO in February 1997. Patients with at least one medical claim with a diagnosis code for migraine or at least two pharmacy claims for sumatriptan, methysergide, ergotamine, dihydroergotamine, or an ergotamine combination product in 1996 or 1997 were eligible for inclusion. A total of 557 patients were included in the analysis. Migraine-related medical costs and total medical costs increased 1.5% and 24.4%, respectively; neither change was statistically significant. Physician office visits related to migraine increased by 7.8%. The number of hospital admissions for the cohort increased from three to five, but hospital costs decreased by 55.0%. The overall costs of medications for migraine therapy decreased by 4.5%. There was an 8.2% increase in prescriptions for drugs to treat migraine but a 40.0% decrease in their cost, primarily because of decreased sumatriptan use. There was a 33.9% increase in prescriptions for medications that could be used as prophylaxis for migraine and a 49.6% increase in their cost. Implementation of a monthly limit on sumatriptan decreased an HMO's pharmacy costs but did not significantly alter migraine-related direct medical costs and health care resource use of patients with migraine.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10565699&dopt=Abstract sumatriptan Imitrex