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Biomedical subjects

M Farré

Publications and source records attributed to M Farré.

At least 55 records · Page 3Linked to original sources
PubMed1999

Quantification of 3,4-methylenedioxymetamphetamine and its metabolites in plasma and urine by gas chromatography with nitrogen-phosphorus detection.

A gas chromatographic method with nitrogen-phosphorus detection involving a solid-liquid extraction phase was developed and validated for the simultaneous quantification of 3,4-methylenedioxymethamphetamine (MDMA) and 3,4-methylenedioxyamphetamine (MDA) in plasma. A modification of this method was validated for the analysis of MDMA, MDA, 4-hydroxy-3-methoxymethamphetamine (HMMA) and, 4-hydroxy-3-methoxyamphetamine (HMA) in urine. Under the analytical conditions described, the limits of detection in plasma and urine were less than 1.6 microg/l and 47 microg/l, respectively, for all the compounds studied. Good linearity was observed in the concentration range evaluated in plasma (5-400 microg/l) and urine (100-2000 microg/l) for all compounds tested. The recoveries obtained from plasma were 85.1% and 91.6% for MDMA and MDA, respectively. Urine recoveries were higher than 90% for MDMA and MDA, 74% for HMMA, and 64% for HMA. Methods have been successfully used in the assessment of plasma and urine concentrations of MDMA and its main metabolites in samples from clinical studies in healthy volunteers.

Chromatography, Gas↗
PubMed1999

Immunomodulating properties of MDMA alone and in combination with alcohol: a pilot study.

Cell-mediated immune response after the administration of MDMA alone and in combination with alcohol was evaluated in a randomized, double-blind, double-dummy, cross-over pilot clinical trial conducted in four healthy MDMA consumers who received single oral doses of 75 mg MDMA (n = 2) or 100 mg MDMA (n = 2), alcohol (0.8 mg/kg), MDMA and alcohol, or placebo. Acute MDMA treatment produced a time-dependent immune dysfunction associated with MDMA plasma concentrations. Although total leukocyte count remained unchanged, there was a decrease in the CD4 T/CD8 T-cell ratio as well as in the percentage of mature T lymphocytes, probably because of a decrease in both the percentage and absolute number of T helper cells. The decrease in CD4 T-cell counts and in the functional responsiveness of lymphocytes to mitogenic stimulation was dose-dependent. The correlation between MDMA pharmacokinetics and the profile of MDMA-induced immune dysfunction suggests that alteration of the immune system may be mediated by the central nervous system. Alcohol consumption produced a decrease in T helper cells, B lymphocytes, and PHA-induced lymphocyte proliferation. Combined MDMA and alcohol produced the greatest suppressive effect on CD4 T-cell count and PHA-stimulated lymphoproliferation. Immune function was partially restored at 24 hours. These results provide the first evidence that recreational use of MDMA alone or in combination with alcohol alters the immunological status.

Adjuvants, Immunologic↗
PubMed1999

Quantification of amphetamine plasma concentrations by gas chromatography coupled to mass spectrometry.

We developed a fast and sensitive method for identification and quantification of plasma concentrations of amphetamine using gas chromatography with mass spectrometry detection (GC-MS). Amphetamine-d8 served as internal standard. The method involves a single extraction procedure and an easy treatment of the samples that allowed no losses during the evaporation process. Derivatisation of amphetamine with N-methyl-bis(trifluoroacetamide), a potent acylating agent, provides many advantages to the method compared with common derivatisation reactions usually used for amphetamines. The limits of detection and quantification following this method were 0.43 and 1.42 ng/ml, respectively. The assay has been successfully employed in the quantification of amphetamine in plasma samples from healthy volunteers at four different doses.

Acetamides↗
PubMed1999

Interspecific hybridization increases transposition rates of Osvaldo.

Several authors have postulated that genetic divergence between populations could result in genomic incompatibilities that would cause an increase in transposition in their hybrids, producing secondary effects such as sterility and therefore starting a speciation process. It has been demonstrated that transposition largely depends on intraspecific hybridization for P, hobo, and I elements in Drosophila melanogaster and for several elements, including long terminal repeat (LTR) and non-LTR retrotransposons, in D. virilis. However, in order to demonstrate the putative effect of transposable elements on speciation, high levels of transposition should also be induced in hybrids between species that could have been originated by this process and that are still able to interbreed. To test this hypothesis, we studied the transposition of the LTR retrotransposon Osvaldo in Drosophila buzzatii-Drosophila koepferae hybrids. We used a simple and robust experimental design, analyzing large samples of single-pair mate offspring, which allowed us to detect new insertions by in situ hybridization to polytene chromosomes. In order to compare transposition rates, we also used a stock recently obtained from the field and a highly inbred D. buzzatii strain. Our results show that the transposition rate of Osvaldo is 10(-3) transpositions per element per generation in all nonhybrid samples, very high when compared with those of other transposable elements. In hybrids, the transposition rate was always 10(-2), significantly higher than in nonhybrids. We show that inbreeding has no effect on transposition in the strains used, concluding that hybridization significantly increases the Osvaldo transposition rate.

Animals↗
PubMed1999

Cardiovascular and neuroendocrine effects and pharmacokinetics of 3, 4-methylenedioxymethamphetamine in humans.

The cardiovascular and neuroendocrine effects and pharmacokinetics of 3,4-methylenedioxymethamphetamine (MDMA, "ecstasy") were assessed in a double-blind, randomized, crossover, and controlled (placebo and amphetamine) clinical trial. Eight men with experience in the recreational use of MDMA participated in four 10-h experimental sessions with a 1-week washout period. Single oral doses of 125 mg and 75 mg of MDMA, 40 mg of amphetamine, and placebo were given. Both MDMA doses significantly increased blood pressure (increases of 40 mm Hg in systolic blood pressure), heart rate (increases of 30 beats/min), and pupillary diameter (mydriasis) as compared with placebo. Oral temperature did not show significant changes in any drug-active condition. Plasma cortisol levels showed a statistically significant increase after MDMA administration. Prolactin levels only increased after high dose of MDMA. Cmax values for 125-mg and 75-mg MDMA doses were 236.4 and 130.9 ng/ml, and Tmax was observed at 2.4 and 1.8 h, respectively. Elimination half-life was 8.6 h and 7.7 h for high and low MDMA doses, respectively. Amphetamine half-life was 15 h. Between 8 and 9% of the doses of MDMA appeared in plasma in the form of 3,4-methylenedioxyamphetamine. The important cardiovascular effects observed after MDMA administration in laboratory conditions at rest (increases of 40 mm Hg in systolic blood pressure and 30 beats/min in pulse rate) could be relevant in terms of toxicity in real-life conditions (e.g., crowded places and physical activity).

3,4-Methylenedioxyamphetamine↗
PubMed1998

Cocaine metabolism in humans after use of alcohol. Clinical and research implications.

The simultaneous administration of cocaine and alcohol implies a pharmacological interaction at pharmacodynamic and pharmacokinetic levels. The latter involves an alteration of cocaine kinetics and metabolism, as well as the biosynthesis of newly active metabolites, such as cocaethylene. Cocaethylene is metabolized along the same pathways as cocaine. Its detection in biological samples indicates the combined consumption of cocaine and alcohol. From epidemiological and toxicological data, it has been suggested that the combination of alcohol and cocaine produces an increased toxicity in addition to behavioral changes. There has been some debate regarding the contribution of cocaethylene to this rise of toxicity. Its pharmacological and toxicological profile is very similar to cocaine. During the interaction of both substances, the rise in cocaine plasma concentrations can explain many of cardiovascular and behavioral effects observed. The contribution of cocaethylene to the interaction is probably minor; its effects are likely additive to those of cocaine. Perhaps its longer elimination half-life can help in understanding long-lasting effects of the alcohol-cocaine combination.

Alcohol Drinking↗
PubMed1998

Abuse liability of flunitrazepam among methadone-maintained patients.

Abuse liability and acute subjective and psychomotor effects of flunitrazepam were assessed in ten methadone-maintained males with history of benzodiazepine and alcohol use, who voluntarily participated in a double-blind, controlled, cross-over, randomized clinical trial. There were six experimental sessions in which a single oral dose of flunitrazepam 1, 2, and 4 mg; triazolam 0.5 and 0.75 mg; and placebo was given. Evaluations included physiological measures; psychomotor performance tasks (simple reaction time, Digit Symbol Substitution Test, balance task, Maddox-wing device); and self-administered subjective effects questionnaires [Addiction Research Center Inventory (ARCI), Profile of Mood States (POMS), a series of visual analog scales (VAS)]. All drugs but flunitrazepam 1 mg caused an impairment of psychomotor tasks. Effects were more evident with the highest doses of both drugs. Only flunitrazepam 4 mg produced a significant decrease in balance time. Triazolam 0.75 mg induced increases in sedation measured by ARCI-PCAG, depression in POMS, and VAS-drowsiness scores. Flunitrazepam 4mg caused euphoria-related effects as measured by increases in ARCI-MBG and "high" scores in the VAS. Our findings of flunitrazepam-induced euphoria in methadone-maintained subjects together with epidemiological evidence of flunitrazepam abuse by opioid dependents, suggest that it may be included in the group of benzodiazepines with a relatively high abuse potential.

Adult↗
PubMed1998

Effect of alendronate on cultured normal human osteoblasts.

Alendronate is an aminobisphosphonate with a potent anti-reabsorptive action that does not appear to interfere with bone mineralization, and is even able to increase bone mineral density in osteoporotic postmenopausal women through a still not fully understood mechanism. This study was conducted to assess the direct effect of alendronate on diverse aspects of normal human osteoblast physiology. For that purpose, the in vitro effect of a wide range of concentrations [from 10(-1) to 10(-12) mol/L] of alendronate on cell viability, proliferation, collagen synthesis, and the mineral-depositing capacity of normal human osteoblasts was tested. Alendronate effects were examined at 48 and 96 h of culture in the presence or absence of fetal calf serum. In vitro alendronate affected osteoblast viability at concentrations equal to or higher than 10(-4) mol/L. At concentrations equal to or higher than 10(-3) mol/L, no viable cells were observed in cultures. In vitro alendronate at concentrations between 10(-5) and 10(-12) mol/L did not have any effect on the proliferative capacity of normal human osteoblasts determined by two different techniques: (1) tritiated thymidine incorporation to DNA and (2) cell counting. Collagen synthesis by normal human osteoblasts showed a tendency to decrease following incubation with alendronate supplemented with fetal calf serum. This decrease was only statistically significant after 96 h of culture; however, a dose-response effect could not be documented. Finally, no effect of alendronate was observed on calcium deposition in vitro by normal human osteoblasts at concentrations equal to or lower than 10(-5) mol/L. In conclusion, the present study shows that alendronate in vitro does not affect viability, proliferation, and mineral deposit capacity of normal human osteoblasts at the concentration at which it inhibits by 50% the resorptive capacity of osteoclasts that for this drug has been reported as 2 x 10(-9) mol/L.

Adult↗
PubMed1997

[Analgesics in the postoperative period of abdominal interventions. The Study Group on Postoperative Analgesia of the Spanish Society of Clinical Pharmacology].

BACKGROUND: Analgesics can avoid postoperative pain. The aim of this study was to evaluate their prescription after abdominal surgery. PATIENTS AND METHODS: Prospective study including patients who had undergone abdominal surgery in two hospitals in Barcelona, in 1993. Prescription and administration of analgesic drugs, and pain severity during the first 48 hours of the postoperative period were evaluated. RESULTS: One hundred and sixty-four patients (83 men) were included. The most frequently prescribed drugs were metamizol (111; 68%), pethidine (83, 51%), and diclofenac (44; 27%). A high percentage of analgesic prescriptions on an "as needed" basis was recorded. Administered doses were lower than those recommended, and lower than those prescribed. Fifty-three percent of patients suffered significant pain during the first day. CONCLUSION: A too low proportion of analgesic drugs is prescribed in a predetermined schedule, in contrast to "as needed" prescription. Opiate derivatives are underused. All analgesic drugs are prescribed at inadequate dosage. This prescription pattern is associated with a high prevalence of postoperative pain.

Abdomen↗
PubMed1997

Tolerability and pharmacokinetics of ebrotidine in healthy subjects given single and repeated oral doses.

The tolerability and safety of ebrotidine (N-[(E)-[[2-[[[2-[(diaminomethylene)amino]-4-thiazolyl]methyl] thio]ethyl]amino]methylene]-4-bromo-benzenesulfonamide, CAS 100981-43-9, FI-3542) and its basic pharmacokinetic parameters were determined after its oral administration to healthy volunteers. Sixteen subjects were selected to participate in two different studies: an increasing single dose study to determine the maximal tolerated dose (from 25 to 1600 mg), and a multiple dose study (stepped doses from 400 to 1600 mg daily for 12 days). The results of the studies showed that ebrotidine has a good tolerability. Vital signs and laboratory tests were not influenced by the study treatment. No clinically relevant adverse effects were reported during the investigation. Ebrotidine reached peak plasma concentrations 2-3 h after oral administration. Its elimination half-life ranged from 9 to 14 h. In conclusion, ebrotidine was well tolerated after administration of oral single doses of up to 1600 mg, and after repeated administration of up to 800 mg/12 h for 12 days.

Administration, Oral↗
PubMed1997

Cocaine and alcohol interactions in humans: neuroendocrine effects and cocaethylene metabolism.

The effects of 100 mg of intranasal cocaine in acute alcohol intoxication (0.8 g/kg) were evaluated in eight experienced and nondependent healthy volunteers in a double-blind double-dummy, controlled, randomized, crossover clinical study. The combination of alcohol and cocaine produced greater increases in HR, rate-pressure product and pleasurable-related subjective effects (euphoria, well-being) compared with the effects of cocaine. The drug combination reduced the alcohol-induced sedation, but feelings of drunkenness were not significantly counteracted. Cardiovascular changes induced by the combination condition caused an increase in myocardial oxygen consumption that may be related to an increased risk of cardiovascular toxicity. The augmented subjective euphoria may explain why the drug combination is more likely to be abused than is cocaine or alcohol alone. Plasma cortisol concentrations were significantly higher after concomitant alcohol and cocaine use than with cocaine alone. The administration of cocaine did not alter alcohol-induced hyperprolactinemia. Although cocaine produced a slight decrease in plasma concentrations of prolactin when administered alone, it did not antagonize the effects of alcohol on prolactin secretion when alcohol and cocaine were given simultaneously. The combination increased cocaine and norcocaine plasma concentrations, and induced the synthesis of cocaethylene and norcocaethylene. The enhancement of cocaine effects in the drug combination may be due to initially increased cocaine plasma levels followed by the additive effect of cocaethylene, although a pharmacodynamic interaction could not be excluded.

Adrenocorticotropic Hormone↗
PubMed1997

Clinical pharmacokinetics and tolerability of dotarizine in healthy subjects after single and multiple oral administration.

Dotarizine is a new diphenylmethylpiperazine derivative with Ca2+ channel blocking properties and inhibitory effects on 5-HT2A and 5-HT2C receptors. Previous pilot studies in healthy volunteers demonstrated a good tolerability after single and multiple dosing. Dotarizine appeared to be rapidly and extensively metabolized to an active compound (FI-6020). We aimed to study the physiologic, subjective and psychomotor acute effects of oral dotarizine after single dose administration, to evaluate the tolerability and safety after multiple dosing over 2 weeks, and to study the pharmacokinetic parameters and linearity after single and multiple administration. Two different studies were carried out in 2 groups of 8 healthy male volunteers. Oral single doses of dotarizine 50, 100 and 200 mg were administered in a randomized, double-blind, crossover, placebo-controlled trial. Oral doses of 50 mg twice daily were administered in an open trial over 14 days. Drug effect assessments included vital signs, collection of adverse events, ECG and blood and urine safety evaluations, subjective effects, psychomotor performance tasks and blood sampling. Dotarizine and its metabolite were determined by gas chromatography with N-P detector. The results showed a good tolerability of dotarizine after single oral doses as well as multiple oral doses over 14 days. No clinically relevant adverse events were reported during the study. The highest single dose (200 mg) produced a slight increase in sedation-related symptoms as well as a slight impairment in psychomotor performance tasks. Dotarizine and its major metabolite proved linear kinetics at single doses. The administration of oral doses of dotarizine 50 mg b.i.d. reached the steady state after the 7th day of treatment. The pharmacokinetic parameters remained similar from day 7 to day 14. The terminal elimination half-life of dotarizine and its metabolite appeared to be between 7 and 12 h.

Administration, Oral↗