sumatriptan, Imitrex
Sumatriptan-induced cerebral vasoconstriction as treatment of experimental intracranial hypertension.

Nilsson F, Nilsson T, Edvinsson L, Rosen I, Bjorkman S, Messeter K, Nordstrom CH.

Department of Anaesthesia and Intensive Care, Malmo University Hospital, Sweden.

BACKGROUND: Increased intracranial pressure (ICP) is a major cause of mortality in severe head injuries and pharmacologically induced cerebral vasoconstriction has been suggested as a possible treatment. In the present study a porcine model of increased ICP was utilized to study the changes in cerebral haemodynamics and energy metabolism induced by a selective 5-hydroxytryptamine1 agonist (sumatriptan). METHODS: ICP was raised by inflation of two balloons covering both parieto-occipital regions extradurally. The animals were randomized into four groups receiving sumatriptan. 0.01 mg.kg-1 (A), 0.03 mg.kg-1 (B), 0.1 mg.kg-1 (C), and 0.5 mg.kg-1 (D) intravenously over 10 min. Measurements of cerebral blood flow (CBF), arterio-venous oxygen content difference (CavO2), and jugular venous pH (vpH) were performed 5, 20, 40, 60, and 75 min after start of the infusion. ICP, mean arterial pressure, and EEG were recorded continuously. Direct effects of sumatriptan were also compared in cortical arteries and veins in vitro. RESULTS: Significant decreases in ICP were obtained in groups A, B, and C while group D exhibited a progressive increase in ICP. Significant reductions in CBF, increase in CavO2, and slowing of EEG were observed in groups B, C, and D. Sumatriptan caused moderate constriction of the arteries and a more pronounced dilatation of veins in vitro. CONCLUSION: The results indicate that a low dose of sumatriptan has the potential to reduce a raised ICP. High doses of sumatriptan cause a further increase of ICP possibly by dilatation of intracerebral veins.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8792894&dopt=Abstract sumatriptan Imitrex



sumatriptan, Imitrex
Sumatriptan use in a large group-model health maintenance organization.

Greiner DL, Addy SN.

Kaiser Permanente, Rockville, MD 20849-6182, USA.

The outcomes of sumatriptan use at a health maintenance organization (HMO) were studied. The study was conducted during one year beginning immediately after sumatriptan was added to the formulary of a large group-model HMO. Subjects were included on the basis of drug-use evaluation criteria, a positive response to the first dose of sumatriptan (administered at the HMO by a nurse), and ability to participate in a telephone survey. Responders to the first dose were eligible to receive up to six doses of sumatriptan for home use. The telephone survey was designed to assess sumatriptan's effects on migraine headache and to capture data on quality of life, perceived problems with sumatriptan, and patient satisfaction. Patients who received sumatriptan between April and September 1993 were interviewed in late September 1993; patients who received sumatriptan between September and April 1994 were interviewed in late April 1994. Of 180 patients surveyed, 160 (89%) had evaluable responses. Migraine headache improved in two thirds of the patients. Sumatriptan was more effective than previously used agents in three fourths. The mean number of migraine headaches per patient per month decreased from 7.4 to 4.2. Quality-of-life indicators, such as time spent with friends, improved in three fourths. Eighty-three percent reported missing fewer days from work. Ninety percent said they would continue to take the drug, despite a 44% incidence of drug-related problems. There were no unexpected problems. A retrospective review showed that utilization of the HMO's resources was reduced with sumatriptan. Placing sumatriptan on an HMO's formulary led to favorable effects on the frequency and severity of migraine headache, patient quality-of-life indicators and productivity, and resource utilization by the organization.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8800968&dopt=Abstract sumatriptan Imitrex



sumatriptan, Imitrex
Fully automated assay for the determination of sumatriptan in human serum using solid-phase extraction and high-performance liquid chromatography with electrochemical detection.

Dunne M, Andrew P.

Drug Metabolism Division, Glaxo Research and Development Limited, Ware, Herts, UK.

A method is described for a fully automated, sensitive, accurate and precise assay for the determination of sumatriptan in human serum. The assay consists of solid-phase extraction followed by reversed-phase HPLC with electrochemical detection. The extraction procedure has been fully automated on a Zymate XP robot linked on-line to the HPLC system. The assay is linear over the analytical range 1-30 ng ml-1 and selective for sumatriptan with respect to endogenous plasma components and GR49336, the major circulating metabolite. The intra-assay data demonstrate a maximum bias and precision across the calibration range of 10% and 6.6% respectively. The inter-assay data demonstrate a maximum bias and precision across the calibration range of 6.7% and 8.8%, respectively. The extraction efficiency of the assay is approximately 90% and is constant across the calibration range. The assay was used for the determination of sumatriptan in serum clinical samples and was shown to be robust in sustained use over several months. The use of a Zymate XP robot allowed complete automation of the assay, which resulted in high-quality, high-throughput analyses.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8807547&dopt=Abstract sumatriptan Imitrex



sumatriptan, Imitrex
Determination of sumatriptan succinate in human plasma by high-performance liquid chromatography with coulometric detection and utilization of solid-phase extraction.

Franklin M, Odontiadis J, Clement EM.

University of Oxford, Department of Psychiatry, Psychopharmacology Research Unit, Littlemore Hospital, Oxford, UK.

Sumatriptan succinate (the analyte) and naloxone (the internal standard) were extracted from plasma with a solid-phase extraction technique. Chromatography and detection were performed by isocratic reversed-phase high-performance liquid chromatography with coulometric end-point detection. The standard curve was linear over the range 0-100 ng/ml of sumatriptan succinate in plasma. The reproducibility (as defined by the coefficient of variation, C.V.) over the range of the standard curve was 4.9-7.3%. The recovery averaged 83%. The sensitivity was 0.25 ng of sumatriptan on column (allowing a concentration of 0.5 ng/ml to be determined from a 1-ml plasma sample volume). Plasma profiles of the analyte following subcutaneous (s.c.) administration in eight normal male volunteers, are presented.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8811457&dopt=Abstract sumatriptan Imitrex



sumatriptan, Imitrex
Influence of vascular tone on vasoconstrictor responses to the 5-HT 1-like receptor agonist sumatriptan in anaesthetised rabbits.

Choppin A, O'Connor SE.

Synthelabo Recherche, Department of Preclinical Research, Bagneux, France.

The cardiovascular profile of the 5-HT1-like receptor agonist sumatriptan has been studied in anaesthetised rabbits pretreated with chlorisondamine (0.5 mg kg-1 i.v.) and enalapril (0.3 mg kg-1 i.v.) to eliminate autonomic reflexes and minimise endogenous vasoconstrictor tone. Under these conditions sumatriptan (2-100 micrograms kg-1 i.v.) produced modest increases in carotid vascular resistance but had no significant influence on heart rate, blood pressure or mesenteric vascular resistance. In a similarly pretreated group of animals in which vasoconstrictor tone was elevated by infusion of angiotensin (100 ng kg-1 min-1 i.v.) sumatriptan caused moderate increases in blood pressure (55 +/- 5 to 65 +/- 5 mm Hg after 25 micrograms kg-1 i.v.) and mesenteric vascular resistance (1.4 +/- 0.2 to 1.6 +/- 0.2 mm Hg min ml-1 after 25 micrograms kg-1 i.v.) and tended to produce a greater carotid vasoconstriction (3.6 +/- 0.5 to 4.7 +/- 0.7 mm Hg min ml-1 after 25 micrograms kg-1). These effects were antagonised by methiothepin 0.3 mg kg-1 i.v. implying the involvement of 5-HT1-like receptor stimulation. Hence, the presence of angiotensin produces a modest amplification of the vasoconstrictor effects of sumatriptan and, in particular, unmasks a constriction of the mesenteric vascular bed. The degree of synergy observed between these two vasoconstrictors was, however, less marked than might have been expected on the basis of previous isolated tissue studies.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8813588&dopt=Abstract sumatriptan Imitrex



sumatriptan, Imitrex
Sumatriptan-nonresponders: a survey in 366 migraine patients.

Visser WH, de Vriend RH, Jaspers NH, Ferrari MD.

Department of Neurology, Leiden (The Netherlands) University Hospital, The Netherlands.

Sumatriptan, notably after subcutaneous administration, is highly effective in the acute treatment of migraine in the majority of patients. The response is consistent within patients and over time. To determine risk factors for nonresponse to sumatriptan, we compared clinical characteristics in responders and nonresponders and, within patients, between attacks with and without response. We found no differences at the strict level of significance (P < 0.001 because of multiple comparisons), but only tendencies for differences (0.001 < P < 0.05) in either the subcutaneous or oral groups. In the subcutaneous group, nonresponders had a higher body mass index, migraine onset at an earlier age, and, most importantly, they treated their migraine attacks earlier. In the oral group, nonresponders had attacks associated with more severe vomiting and photophobia, more often went to sleep or rest, and more frequently experienced initial worsening of the headache after sumatriptan administration. Within patients, no differences were found between attacks with and without response. In conclusion, we found few, if any, clinically relevant risk factors for nonresponse to sumatriptan. Administration of sumatriptan too early was the strongest indicator and should be avoided.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8824001&dopt=Abstract sumatriptan Imitrex



sumatriptan, Imitrex
Pattern of sumatriptan use and overuse in general practice.

Ottervanger JP, Valkenburg HA, Grobbee DE, Stricker BH.

Netherlands Centre for Monitoring of Adverse Reactions to Drugs, Rijswijk, The Netherlands.

OBJECTIVE: To investigate the frequency of use and misuse of sumatriptan, and to explore the characteristics of patients reporting overuse. SETTING: A postmarketing cohort study on adverse reactions to sumatriptan, performed with the assistance of drug-dispensing general practitioners in the Netherlands. METHODS: Questionnaires were sent to patients on sumatriptan of drug-dispensing general practitioners in the Netherlands. Use of sumatriptan was classified into five groups: < 1, 1-10, 11-20 and 21-30 times per month and a group of patients who reported daily use of sumatriptan more than 10 times per week. Patients in the latter group were regarded as "overusers". RESULTS: The request to the 1720 patients yielded a response rate of 1202 (70%). Of 952 (79%) of these patients, details of their sumatriptan intake were available. Most patients (718, 75%) took sumatriptan 1-10 times each month. However, 36 patients (4%, 95% CI 2.8-5.2%) took sumatriptan daily or more than 10 times each week. The group with the highest intake consisted mainly of males, and many patients who reported a poor efficacy of sumatriptan. Age was not related to use of sumatriptan. CONCLUSIONS: A small group of patients (4%) used sumatriptan too often. A high intake was associated with both male gender and a reported poor efficacy of sumatriptan, but not with age, reported adverse reactions, or headache attributed to sumatriptan. It is important to explain to patients that sumatriptan is only for the treatment of acute attacks, and not for prophylactic use. Drug consumption patterns have to be evaluated, in particular in patients who report low efficacy of sumatriptan.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8839655&dopt=Abstract sumatriptan Imitrex