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Magí Farré

Publications and source records attributed to Magí Farré.

36 records · Page 2Linked to original sources
PubMed2004

Putting clinical pharmacology in context: the use of popular movies.

The usefulness of movies to illustrate the psychological and sociological conflicts of medical practice is widely recognized. However, the use of popular movies to teach less oriented medical sciences, such as pharmacology is not so common. In the present review, we report the use of three films (Awakenings, Lorenzo's Oil, and Miss Evers' Boys) as a teaching tool to allow students to better understand some conflicts which appear in the domain of clinical pharmacology. These movies may help to introduce some relevant topics such as the difficulties of planning and performing clinical research with new drugs, the need of considering bioethical principles when doing research with human beings, and the social and psychological aspects of drug therapy. The films may increase the motivation of students to understand clinical pharmacology principles and may become a driving force for an increased desire to learn.

Education, Medical, Undergraduate↗
PubMed2004

Clinical pharmacokinetics of amfetamine and related substances: monitoring in conventional and non-conventional matrices.

Consumption of amfetamine-type stimulants, including classical amfetamines and 'designer drugs', has been recognised as one of the most significant trends in drug abuse at the end of the past century and at the beginning of the current one. The first cause is the increasing consumption amongst youth of methylenedioxy- and methoxy-substituted amfetamines, of which the pharmacology in humans is currently under investigation. Secondly, the abuse of more classical amfetamines, such as amfetamine itself and metamfetamine, continues to be highly prevalent in some geographical regions. Amfetamines are powerful psychostimulants, producing increased alertness, wakefulness, insomnia, energy and self-confidence in association with decreased fatigue and appetite as well as enhanced mood, well-being and euphoria. From a clinical pharmacokinetic perspective, amfetamine-type stimulants are rather homogeneous. Their oral bioavailability is good, with a high distribution volume (4 L/kg) and low binding to plasma proteins (less than 20%). The elimination half-life is 6-12 hours. Both hepatic and renal clearance contribute to their elimination from the body. Hepatic metabolism is extensive in most cases, but a significant percentage of the drug always remains unaltered. Amfetamine and related compounds are weak bases, with a pKa around 9.9, and a relatively low molecular weight. These characteristics allow amfetamine-type stimulants to diffuse easily across cell membranes and lipid layers and to those tissues or biological substrates with a more acidic pH than blood, facilitating their detection in alternative matrices at relatively high concentrations. In most cases, the concentrations found are higher than expected from the Henderson-Hasselbach equation. Drug monitoring in non-conventional biological matrices (e.g. saliva, hair, nails, sweat) has recently gained much attention because of its possible applications in clinical and forensic toxicology. An individual's past history of medication, compliance or drug abuse can be obtained from testing of hair and nails, whereas data on current status of drug use can be provided by analysis of sweat and saliva. Because of the physicochemical properties of amfetamine-type stimulants, this group of drugs is one of the most suitable for drug testing in non-conventional matrices.

Amphetamine↗
PubMed2004

Stereochemical analysis of 3,4-methylenedioxymethamphetamine and its main metabolites in human samples including the catechol-type metabolite (3,4-dihydroxymethamphetamine).

3,4-Methylenedioxymethamphetamine (MDMA; "ecstasy") is a designer drug commonly misused in large segments of young populations. MDMA is usually formulated in tablets of its racemate (1:1 mixture of its enantiomers) in doses ranging from 50 to 200 mg. MDMA has an enantioselective metabolism, the (S)-enantiomer being metabolized faster than the (R)-enantiomer. Different pharmacologic properties have been attributed to each enantiomer. The carbon responsible for MDMA chirality is preserved along its metabolic disposition. An analytical method has been developed to determine MDMA enantiomers and those from its major metabolites, 3,4-methylenedioxyamphetamine (MDA), 3,4-dihydroxymeth-amphetamine (HHMA), and 4-hydroxy-3-methoxymethamphet-amine (HMMA). It has been applied to the analysis of plasma and urine samples from healthy recreational users of MDMA who participated voluntarily in a clinical trial and received 100 mg (R,S)-MDMA. HCl orally. (R)/(S) ratios both in plasma (0-48 h) and urine (0-72 h) for MDMA and MDA were >1 and <1, respectively. Ratios corresponding to HHMA and HMMA, close to unity, deviate from theoretical expectations and are most likely explained by the ability of MDMA to autoinhibit its own metabolism. The short elimination half-life of (S)-MDMA (4.8 h) is consistent with the subjective effects and psychomotor performance reported in subjects exposed to MDMA, whereas the much longer half-life of the (R)-enantiomer (14.8 h) correlates with mood and cognitive effects experienced on the next days after MDMA use.

3,4-Methylenedioxyamphetamine↗
PubMed2003

Development and validation of a gas chromatography-mass spectrometry assay for hair analysis of amphetamine, methamphetamine and methylenedioxy derivatives.

A procedure based on gas chromatography-mass spectrometry (GC-MS) is described for the determination of amphetamine, methamphetamine, 3,4-methylenedioxyamphetamine (MDA), 3,4-methylenedioxymethamphetamine (MDMA, ecstasy), 3,4-methylenedioxyethylamphetamine (MDE or MDEA) and N-methyl-1-(3,4-methylenedioxyphenyl)-2-butanamine (MBDB) in hair. Hair samples were digested with 1 M sodium sulfide at 37 degrees C (by shaking for 3 h and was kept at room temperature overnight), and extracted with two sequential extraction procedures: liquid-liquid extraction with tert-butyl methyl ether and solid-phase extraction with Bond-Elut Certify columns. Extracted analytes were derivatised with N-methyl-bis(trifluoroacetamide), separated by a 5% phenylmethylsilicone column and determined by a mass spectrometer detector in selected ion monitoring mode. A good reproducibility (intra-assay R.S.D.=1.5-15.7%), accuracy (intra-assay error = 2.0-11.7%) and sensitivity (LOD=0.03-0.08 ng/mg hair) were attained. The method was successfully applied to the analysis of the proximal (1 cm) hair segment to assess recent self-reported use in "ecstasy" consumers. Otherwise, further studies are needed to validate methodology developed in case of amphetamine consumption.

Amphetamine↗
PubMed2003

Drug addiction.

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Animals↗
PubMed2003

Placebo effect and placebos: what are we talking about? Some conceptual and historical considerations.

Placebos and the placebo effect have always been present in medical history. However, they have not received the same consideration over the years. Somewhere between art and science, the placebo historical references come from Ancient Egypt and cross over the major civilisations, beliefs and scientific advances. The use of placebo as a methodological tool has assumed a leading role in the last 50 years and has become an important role in controlled clinical trials, the main element of the "evidence-based-medicine" paradigm. Knowledge of the conceptual and historical considerations of placebo may help to understand its role in medical practice. Even without a consensual definition, and assuming that the placebo effect does not seem to be fully dependent on a placebo administration, one issue seems unquestionable: the placebo effect is present in clinical practice and in clinical trials, no matter which name we choose to call it.

Clinical Trials as Topic↗
PubMed2003

[Drug Design].

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Drug Design↗
PubMed2003

Quantitative determination of paroxetine and its 4-hydroxy-3-methoxy metabolite in plasma by high-performance liquid chromatography/electrospray ion trap mass spectrometry: application to pharmacokinetic studies.

A high-performance liquid chromatography (HPLC) method with tandem mass spectrometric detection is described for the determination of paroxetine, an antidepressant drug, and its metabolite (3S,4R)-4-(4-fluorophenyl)-3-(4-hydroxy-3-methoxyphenoxymethyl)piperidine (HM paroxetine) in human plasma. Plasma samples were hydrolysed with hydrochloric acid and then analytes were extracted with ethyl acetate at alkaline pH. Extracts were analysed by HPLC coupled to an atmospheric pressure ionisation-electrospray (ESI) interface and an ion trap mass spectrometer. Chromatography was performed on a reversed-phase column using acetonitrile/0.02% formic acid (66:34, v/v) as a mobile phase. The mass spectrometer was operated in the multiple reaction monitoring mode. The method was validated over concentration ranges of 0.75-100 microg/L and 5-100 microg/L for paroxetine and HM paroxetine, respectively. Mean recoveries of 77% for paroxetine and 76% for HM paroxetine were found, with precision always better than 15%. The limits of detection and quantification were 0.20 and 0.70 microg/L for paroxetine, and 0.70 and 2.20 microg/L for its metabolite. The method was applied to the analysis of plasma samples obtained from nine healthy male volunteers administered with a single oral dose of 20 mg paroxetine. After the 20-mg dose, the mean peak plasma concentration was 8.60 microg/L for paroxetine and 92.40 microg/L for HM paroxetine showing a tenfold ratio between the metabolite and the parent drug along the entire time-concentration curve.

Administration, Oral↗
PubMed2003

Stereochemical analysis of 3,4-methylenedioxymethamphetamine and its main metabolites by gas chromatography/mass spectrometry.

3,4-Methylenedioxymethamphetamine (MDMA, ecstasy) is consumed as the racemate but some metabolic steps are enantioselective. In addition, chiral properties are preserved during MDMA biotransformation. A quantitative analytical methodology using gas chromatography/mass spectrometry (GC/MS) to determine enantioselective disposition in the body of MDMA and its main metabolites including 3,4-methylenedioxyamphetamine (MDA), 4-hydroxy-3-methoxymethamphetamine (HMMA), and 4-hydroxy-3-methoxyamphetamine (HMA) was developed. Plasma and urine samples were collected from a male volunteer. The analysis of MDMA, MDA, and 4-hydroxy-3-methoxy metabolites by GC/MS required a two-step derivatization procedure. The first step consisted of derivatization of the amine with enantiomerically pure Mosher's reagent ((R)-MTPCl). Triethylamine was used as a base to neutralize hydrochloric acid formed during the reaction allowing quantitative derivatization, which resulted in a substantial improvement in the sensitivity of the method compared with other previously described techniques. Further treatment with ammonium hydroxide was required since both amine and hydroxyl groups underwent derivatization in the reaction. Ammonium hydroxide breaks bonds formed with hydroxyl groups without affecting amine derivatives. The second derivatization step using hexamethyldisilazane was needed for metabolites containing phenol residues. This derivatization method permitted the stereochemically specific study of MDMA and its main monohydroxylated metabolites by GC/MS. A detailed study of the chemical reactions involved in the derivatization steps was indispensable to develop a straightforward, sensitive, and reproducible method for the analysis of the parent drug compound and its metabolites.

3,4-Methylenedioxyamphetamine↗
PubMed2002

Retention rate and illicit opioid use during methadone maintenance interventions: a meta-analysis.

The efficacy of methadone maintenance in opioid addiction was assessed in terms of programme retention rate and reduction of illicit opioid use by means of a meta-analysis of randomised, controlled and double blind clinical trials. The results were compared with interventions using buprenorphine and levo-acetylmethadol (LAAM). Trials were identified from the PubMed database from 1966 to December 1999 using the major medical subject headings 'methadone' and 'randomised controlled trial'. Data for a total of 1944 opioid-dependent patients from 13 studies were analysed. Sixty-four percent of patients received methadone, administered either as fixed or adjusted doses. Thus, 890 patients received > or = 50 mg/day (high dose group) and 392 were given < 50 mg/day (low dose group). Of 662 controls, 131 received placebo, 350 buprenorphine (265 at doses > or = 8 mg/day and 85 at doses < 8 mg/day) and 181 LAAM. High doses of methadone were more effective than low doses in the reduction of illicit opioid use (odds ratio [OR] 1.72, 95% confidence interval [CI] 1.26--2.36). High doses of methadone were significantly more effective than low doses of buprenorphine (< 8 mg/day) for retention rates and illicit opioid use, but similar to high doses of buprenorphine (> or = 8 mg/day) for both parameters. Patients treated with LAAM had more risk of failure of retention than those receiving high doses of methadone (OR 1.92, 95% CI 1.32--2.78). It is proposed that in agonist-maintenance programmes, oral methadone at doses of 50 mg/day or higher is the drug of choice for opioid dependence.

Buprenorphine↗
PubMed2002

Postprandial and short-term effects of dietary virgin olive oil on oxidant/antioxidant status.

It is generally believed that virgin olive oil consumption has beneficial effects, but little is known about its effects postprandially on oxidant/antioxidant status. The aim of this study was to determine changes in oxidative stress biomarkers and lipid profile after a single dose of virgin olive oil and after 1 wk of daily consumption. Sixteen subjects (9 men, 7 women) ingested 50 mL of virgin olive oil in a single dose. Blood samples were collected from 0 to 24 h. Thereafter, 14 participants (8 men, 6 women) followed a 1-wk 25 mg/d virgin olive oil dietary intervention. Blood samples were collected at the end of this period. Serum TAG (P = 0.016), plasma FA (P < 0.001), and lipid peroxidation products in plasma (P< 0.001) and VLDL (P = 0.007) increased, reaching a peak at 4-6 h, and returning to baseline values at 24 h after oil ingestion. The opposite changes were observed in plasma glutathione peroxidase (P = 0.001) and glutathione reductase (GR) (P = 0.042). No changes in LDL lipid peroxidation or resistance to oxidation were observed postprandially. At 24 h, plasma oleic acid remained increased (P < 0.05) and resistance of LDL to oxidation improved (P < 0.05). After 1 wk of virgin olive oil consumption, plasma oleic acid (P = 0.031), resistance of LDL to oxidation (P< 0.05), and plasma GR activity (P = 0.005) increased. These results indicate that changes in oxidant/antioxidant status occur after oral virgin olive oil. Virgin olive oil consumption could provide short-term benefits for LDL resistance to oxidation and in glutathione-related enzyme activities.

Adult↗
PubMed2002

Plasma and urinary markers of oral testosterone undecanoate misuse.

Orally administered testosterone undecanoate (TU), an anabolic, androgenic steroid, can potentially be abused by athletes. Indirect evidence for detecting oral TU intake could be deduced from the changes in steroid profile post-administration. Direct evidence could be obtained by detection of unchanged TU in plasma. To this end, both urinary and plasma steroid profiles of six healthy male subjects given a single oral dose of 120 mg of TU were studied by gas chromatography/mass spectrometry (GC/MS) and gas chromatography/tandem mass spectrometry (GC/MS/MS). The increased concentration of glucuronidated testosterone in plasma appears to be the most characteristic sign of oral TU intake. The testosterone glucuronide (TG)/nonconjugated testosterone (T) ratio, TG/17-hydroxyprogesterone (17OHP) ratio, and TG/luteinizing hormone (LH) ratio were observed to be significantly elevated above their basal levels for 10 h, 10 h, and 6 h, respectively. Urinary ratios of TG/epitestosterone glucuronide (EG) were found to be higher than the cut-off value of 6 for the period 4 approximately 8 h post-administration, but only in three subjects. One subject failed to respond with respect to all of the above-mentioned indirect markers, as TG was not significantly increased in either plasma or urine. Unchanged TU was directly detected in plasma of all six subjects from 1 approximately 1.5 h to 4 approximately 6 h after oral TU intake by GC/MS/MS, providing unequivocal proof of exogenous testosterone intake. Distinct and complementary markers for detecting oral TU intake could be obtained from plasma and urine, respectively.

Administration, Oral↗
PubMed2002

Synthesis and capillary electrophoretic analysis of enantiomerically enriched reference standards of MDMA and its main metabolites.

Enantiomerically-enriched (S)-3,4-methylenedioxymethamphetamine (MDMA) and its main metabolites (S)-4-hydroxy-3-methoxymethamphetamine (HMMA) and (S)-3,4-dihydroxymethamphetamine (HHMA) were prepared for unequivocal identification of the differential enantioselective metabolism of these compounds as well as for its application in the analysis of biological samples. Capillary electrophoresis with cyclodextrin derivatives and a chemical correlation of (S)-MDMA, (S)-HMMA and (S)-HHMA has been performed to assign the absolute stereochemistry of major isomers in analytical standards enriched with such enantiomers.

Deoxyepinephrine↗
PubMed2002

Determination of MDMA and its metabolites in blood and urine by gas chromatography-mass spectrometry and analysis of enantiomers by capillary electrophoresis.

A gas chromatography-mass spectrometry (GC-MS) method was used for the simultaneous quantitation of 3,4-methylenedioxymethamphetamine (MDMA) and the 3,4-methylenedioxyamphetamine (MDA), 4-hydroxy-3-methoxymethamphetamine (HMMA), and 4-hydroxy-3-methoxyamphetamine (HMA) metabolites in plasma and urine samples after the administration of 100 mg MDMA to healthy volunteers. Samples were hydrolyzed prior to a solid-phase extraction with Bond Elut Certify columns. Analytes were eluted with ethyl acetate (2% ammonium hydroxide) and analyzed as their trifluoroacyl derivatives. Linear calibration curves were obtained at plasma and urine concentration ranges of 25-400 ng/mL and 250-2000 ng/mL for MDMA and HMMA, and of 2.5-40 ng/mL and 100-1000 ng/mL for MDA and HMA. Following the same urine preparation procedure but without the derivatization step, a capillary electrophoresis (CE) method for enantiomerical resolution of compounds was developed using (2-hydroxy)propyl-beta-cyclodextrin at two different concentrations (10 and 50mM in 50mM H3PO4, pH 2.5) as chiral selector. Calibration curves for the CE method were prepared with the corresponding racemic mixture and were linear between 125 and 2000 ng/mL, 50 and 1000 ng/mL, and 125 and 1500 ng/mL for each enantiomer of MDMA, MDA, and HMMA, respectively. Stereoselective disposition of MDMA and MDA was confirmed. HMMA disposition seems to be in apparent contradiction with MDMA findings as the enantiomer ratio is close to 1 and constant over the time.

3,4-Methylenedioxyamphetamine↗
PubMed2002

3,4-Methylenedioxymethamphetamine (ecstasy) and alcohol interactions in humans: psychomotor performance, subjective effects, and pharmacokinetics.

3,4-Methylenedioxymethamphetamine (MDMA) is frequently consumed in association with alcohol. The effect of this combination in humans has not been previously investigated. Nine male healthy volunteers received single oral doses of 100 mg of MDMA plus 0.8 g/kg ethanol, 100 mg of MDMA, 0.8 g/kg of ethanol, and placebo in a double blind, double dummy, randomized crossover trial. Measurements included psychomotor performance, subjective effects, and pharmacokinetics. Plasma concentrations of MDMA showed a 13% increase after the use of alcohol, whereas plasma concentrations of alcohol showed a 9 to 15% decrease after MDMA administration. The MDMA-alcohol combination induced longer lasting euphoria and well being than MDMA or alcohol alone. MDMA reversed the subjective sedation induced by alcohol but did not reduce drunkenness feelings. MDMA did not reverse the actions of alcohol on psychomotor abilities. Combined use of MDMA and alcohol causes dissociation between subjective and objective sedation. Subjects may feel euphoric and less sedated and might have the feeling of doing better, but actual performance ability continues to be impaired by the effect of alcohol. Confirmation of these findings in further studies will be highly relevant in terms of road safety.

Adult↗
PubMedDate not supplied

Usefulness of sweat testing for the detection of MDMA after a single-dose administration.

Nine healthy male subjects and recreational users of 3,4-methylenedioxymethamphetamine (MDMA) participated in a study aimed to assess the usefulness of sweat testing for the detection of MDMA after a single 100-mg dose. Sweat was collected for up to 24 h with the PharmChek sweat patches from which drugs were eluted and then analyzed by immunoassay and gas chromatography-mass spectrometry using deuterated internal standards. The usefulness of a rapid onsite test, the Drugwipe immunochemical strip test, was also assessed. In the sweat patches, MDMA was detected as early as 1.5 h after consumption and peaked at 24 h. Intersubject variability was large; peak MDMA concentrations for the same dose varied in magnitude 30-fold. MDMA concentrations ranged between 3.2 and 1326.1 ng/patch. Only traces of the minor metabolite 3,4-methylenedioxyamphetamine were detected. In all subjects, the onsite test with the Drugwipe was positive at 1.5 h (peak time of MDMA plasma concentration). However, few false-negative results (18%) appeared in the first 6 h after administration. Both sweat patch testing and the onsite sweat strip test may find useful application for noninvasive monitoring of MDMA abuse in sweat.

3,4-Methylenedioxyamphetamine↗