Pharmacokinetics of sumatriptan in non-respondent and in adverse drug reaction reporting migraine patients

Sumatriptan is a selectiveagonist of 5HT1 (1B/1D) receptors,which has proved to be effectiveand safe for the acute treatment ofmigraine attacks. Nevertheless, itsuse by migraine sufferers is stilllimited and some patients consideradverse reactions related to sumatriptan,especially chest symptoms,unacceptable even if not serious.Moreover, in clinical trials, almostone third and one sixth of patients,respectively, fail to experienceheadache relief either after oral orafter subcutaneous sumatriptanadministration. Our aim was to verifywhether differencies in sumatriptanpharmacokinetics couldexplain non-response and/oradverse drug reactions. Sumatriptanlevels were determined by HPLCwith electrochemical detection.Pharmacokinetic parameters werecalculated using a computer program(PK Solutions 2.0; non compartmentalPharmacokinetics DataAnalysis). After oral administration,sumatriptan is rapidly absorbed andsometimes displays multiple peaksof plasma concentration. This “multiplepeaking” gives rise to considerableinter-subject variability inthe time of reaching maximumplasma concentration.Pharmacokinetic parameters ofsumatriptan, both after oral andsubcutaneous administration, weresimilar in the three patient groups.Blood pressure and heart rate didnot show any significant differencesbetween groups. Pharmacokineticparameters and bioavailability ofsumatriptan did not seem to be correlatedeither to the lack of efficacyor the appearance of side effects.These results could depend on thelimited number of patients studied

A family outbreak of tinea capitis due to Trichophyton violaceum in Michigan. Its control with griseofulvin

An outbreak of tinea capitis caused by Trichophyton violaceum in five siblings of a family of eight in Michigan and its control with griseofulvin are described.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/43276/1/11046_2005_Article_BF02145740.pd

Variability of oral sumatriptan pharmacokinetics in migraine patients

Sumatriptan was the first selective serotonin (5-HT) 1B/1D agonist for the acute treatment of migraine attacks. It is thought to relieve migraine attacks by several mechanisms including cranial vasoconstriction and peripheral and central neural inhibition. Sumatriptan has proved to be effective and generally well tolerated in the absence of cardiovascular disease . Nevertheless, its use by migraine sufferers is still limited, approximately 40% of patients using only one prescription of this drug. Reason for terminating use after only one prescription is inefficacy and/or side effects in the majority (78%) of patients . Objectives: To evaluate oral bioavailability and pharmacokinetic profiles of sumatriptan in migraine patients. Methods: We studied 10 migraine patients (8 F, 3 M; mean age 45.3+8.1 years, range 34-60 years) twice, after oral (100 mg) and after subcutaneous (6 mg) administration of sumatriptan. A 1-week washout period was allowed between the administration of the two formulations. Patients were studied in headache free intervals. Blood samples were taken at baseline, at 15, 30, 45, 60, 90, 120, 180, 240, 300 and 360 min. after oral administration, and at baseline, at 5, 10, 15, 20, 25, 30, 60, 90, 120 and 180 min. after subcutaneous injection. Sumatriptan concentrations were determined by HPLC with electrochemical detection. Pharmacokinetic parameters were calculated by means of the P K Solutions 2.0 program. The value of AUC obtained after subcutaneous administration was assumed correspond to 100% of bioavailability and relative oral bioavailability was calculated referred to this value. Results: Following administration of an oral dose of 100 mg, plasma concentrations of sumatriptan showed large differences among patients and two subjects had multiple peaks. In particular (Fig. 1), 5 patients (these subjects will be referred to as group A hereinafter) absorbed the drug faster (Tmax <120 min.), and achieved plasma levels significantly higher (soon after 45 minutes and up to 90 minutes) than the other 5 patients (hence forth, these last patients with Tmax >180 min will be referred to as group B). Notably, the systemic exposure to sumatriptan in the first 2 hours (which are the most important for rapid onset of action and for the antimigraine efficacy) was significantly greater in group A than in group B, as shown by AUC0-2 value in group A (3.174.2+1186 ng/min/ml) which is double the value in group B (1530.9+256 ng/min/ml). On the other hand, after subcutaneous administration of 6 mg of sumatriptan, the profile of the curves was similar in all patients, and there were no differences in pharmacokinetics between group A and group B. Conclusions: Since Tmax is a key variable in migraine response, and migraine relief is related to the systemic exposure to the drug in the first 2 hours after dosing, patients with slow rate and low extent of absorption of the drug in this interval of time could have poor benefit after oral sumatriptan administration. These patients could instead obtain more migraine relief using injection formulation of the drug, since there are no significant differences in pharmacokinetics after subcutaneous administration of sumatriptan. Our findings have the limitation of having been obtained in a small number of patients; however, they could explain the variability of outcomes observed with the different formulations of sumatriptan. Indeed, almost one third of patients in clinical trials fail to have headache relief after oral administration, while only one sixth of patients fail to have headache relief after subcutaneous administration. It is precisely the marked variability in the rate and extent of sumatriptan absorption after oral administration that we observed in clinical practice which could have an impact on sumatriptan response and, as a consequence, in some patients’ disaffection with this drug

Deacidification of vegetable oils for biodiesel production by heterogeneus catalysis using low temperature and pressure

The deacidification reaction of vegetable oils for biodiesel production has been performed by esterification with methanol and ethanol using commercial acid catalysts, i.e. Amberlyst\uae (Rhom and Haas). The aim of the work has been the use of low temperature (< 70\ub0C) and room pressure for the process. The research has dealt with different parameters: the kind of vegetable oil, the type and the activation of catalyst, the amount of Free Fatty Acids in the oil, the alcohol, the ratios oil/alcohol/catalyst. The process has been performed both in batch and in continuous way and the time of life of the catalyst has been studie

Complessi metalli pesanti-amminoacidi-minerali delle argille nei terreni sottostanti le discariche RSU

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A key process of aroma evolution: fatty acid ss-oxidation in Parmesan cheese ripening

A study is described in which solid phase microextraction was used to investigate aroma evolution during the ripening of Parmesan cheese. The predominant organic acids produced during ageing were hexanoic and butanoic acids, whereas the major ketone was 2-heptanone. Metabolic processes leading to generation of these compounds are discussed. It is suggested that measurement of volatile compounds could be used as an indication of Parmesan cheese ripeness

Volatile components of Grana Parmigiano-Reggiano type hard cheese

GC-MS analysis of volatile components of Grana Parmigiano-Reggiano type Italian hard cheese was performed by solid phase micro extraction (SPME) and Purge & Trap (PT) methods. Half of the 24 samples analysed were produced in flat land ( < 90 in over sea level), the other half in mountain (90-600 in) regions, by small to medium cheese factories. The composition of the volatile components reveals more dependence on the individual factories than on the geographic location. Ripening increases the difference among samples