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Biomedical subjects

J Segura

Publications and source records attributed to J Segura.

At least 163 records · Page 9Linked to original sources
PubMed1989

Effect of quinolones on caffeine disposition.

Six healthy volunteers received a single caffeine dose after pretreatment with norfloxacin, pipemidic acid, or placebo in a crossover, randomized, single-blind clinical trial. Quinolones altered the pharmacokinetics of caffeine, with a significant increase in the AUCs and a decrease in plasma clearance. The elimination half-life increased significantly with pipemidic acid. The apparent volume of distribution, mean renal clearance, and time to reach maximum caffeine concentrations remained unaltered. There was a decline in caffeine metabolite levels in the 24-hour urine samples for both quinolone treatments, suggesting that pipemidic acid and, to a lesser degree, norfloxacin inhibit metabolism of the N-demethylation pathways of caffeine. The practical consequence of this observation could be caffeine accumulation during repeated intake of coffee. In two additional healthy volunteers under a controlled multiple-dose regimen of caffeine ingestion, administration of pipemidic acid for 2 days caused a fourfold increase in the plasma concentrations of caffeine.

Adult↗
PubMed1989

Efficacy of ethanolamine and polidocanol in the eradication of esophageal varices. A prospective randomized trial.

A prospective randomized trial has been undertaken to compare the efficacy of two sclerosing agents, Ethanolamine oleate (Et) and Polidocanol (Pl), in the eradication of esophageal varices (EV). Fifty consecutive cirrhotic patients, 22 in the Et and 28 in the Pl group, were included. Clinical data were comparable in both groups. Eradication of the EV was achieved in 81% (18/22) in the Et group and 64.1% (18/28) in the Pl group (p = NS). There was a significant difference in the rate of rebleeding (4 episodes in 3 patients in the Et group and 18 episodes in 13 patients in the Pl group, p less than 0.05). No differences were noted in the number of other complications or mortality. Both sclerosants have proved useful in the eradication of EV, but Et was superior to Pl in the preventation of recurrent bleeding in the course of repeated endoscopic injection sclerotherapy (EIS).

Esophageal and Gastric Varices↗
PubMed1989

The influence of structure on the accumulation of caffeine induced by methyl xanthine derivatives.

In rats given caffeine (25 mg kg-1 p.o.) and 1,3,8-trisubstituted xanthine (1,3,8-TSX) derivatives (10 mg kg-1 p.o.) the accumulation of the former in plasma was 300% higher than that in control animals given caffeine alone. The effect on caffeine accumulation appears to be independent of the nature of the N3 substituent and its absence in rats given 1,3-disubstituted xanthines (1,3-DSX) instead of 1,3,8-TSX suggests that the presence of the C8-methyl group in the latter compounds is responsible for the accumulation phenomenon. The results of our previous work imply that these observations in this rat model can be extrapolated to man.

Animals↗
PubMed1989

Proficiency testing on drugs of abuse: one year's experience in Spain.

The need for external quality control for drugs-of-abuse urinalysis has long been recognized. Based on experiences in other countries, a proficiency testing program has been introduced recently in Spain. Sterile urine samples containing different concentrations of drugs and metabolites are analyzed by participating laboratories four times a year. Comprehensive educational reports reviewed by an advisory committee are released after each batch analysis. The first year's results verify (a) a beneficial influence of the program in regard to reducing errors when adequate techniques are used, (b) the need for using confirmatory techniques, and (c) the importance of experience and laboratory resources for optimizing results. The educational aspects of the program for the second year are stressing especially the in situ training of analysts and the supply of solutions of drugs and metabolites to be used as reference standards.

Accreditation↗
PubMed1988

Detection and quantification of non-steroidal anti-inflammatory agents by gas chromatography/mass spectrometry: diclofenac.

A sensitive and reliable gas chromatography/mass spectrometric assay for diclofenac in plasma using selected ion monitoring is described. The procedure is based on the acidic extraction of diclofenac and ketoprofen (internal standard) with toluene. Both compounds are converted into their ethyl ester derivatives with ethanol containing 0.5% (v/v) sulphuric acid. No internal cyclization to indolone side product is produced in these conditions. The ions monitored are m/z 214 for diclofenac and m/z 209 for ketoprofen. The main recovery of diclofenac added to plasma has been estimated around 84.6% (120 ng ml-1, n = 4). The intra-assay and inter-assay variability were 1.9% and 10.3%, respectively. The sensitivity was lower than 2 ng ml-1. The applicability of the assays to study the bioavailability of two formulations in a multiple-dosage trial is described. The method has been used in more than 600 determinations without any interference.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1988

Optimization of the quantitative analysis of the major cannabis metabolite (11-nor-9-COOH-delta 9-tetrahydrocannabinol) in urine by gas chromatography/mass spectrometry.

A gas chromatographic/mass spectrometric electron impact method is presented for the detection and quantification of 11-nor-9-carboxy-delta 9-tetrahydrocannabinol (THC-COOH) in urine, for use in the confirmation of presumptive results obtained by other techniques. Four extraction procedures, two solid-liquid and two liquid-liquid, have been compared. A comparison of two trimethylsilylating methods demonstrates that the best results are obtained by the use of a mixture containing N-methyl-N-trimethylsilyl-trifluoroacetamide, trimethyliodosilane and dithioerithritol (100:0.2:1) v/v/w. The use of ketoprofen as a new internal standard for the quantification of THC-COOH has proved to be very effective. Both spiked samples and samples from cannabis users have been successfully analysed. It has also been demonstrated that the presence of other drugs of abuse in urine samples do not interfere with cannabis quantification by the method reported here.

Dronabinol↗
PubMed1988

Comprehensive gas chromatographic analysis of heroin street samples.

A comprehensive analytical approach for heroin street samples is faced with problems associated with differences in polarity, stability and physico-chemical properties of the various substances present. Difficulties with carbohydrates are of particular concern. In this method, which is suitable for screening purposes, 10 mg of sample is dissolved in acetonitrile-trifluoroacetic acid in the presence of methyl orange. Derivatization is then accomplished by O-silylation (MSTFA) and N-trifluoroacetylation (MBTFA). Compounds were detected by flame ionization after a capillary gas chromatographic separation and produced well shaped peaks for the majority of substances. Sugars gave multiple but reproducible chromatographic peaks. By direct derivatization of another aliquot of the solid sample a single predominant chromatographic peak can be obtained for sugars using MSTFA with MBTFA. Alternatively the more potent reagent MSHFB gives highly reproducible results.

Journal Article↗
PubMed1988

Analysis of naltrexone urinary metabolites.

A reversed-phase HPLC method using ion-pair formation has been developed for the simultaneous determination of naltrexone and three urinary metabolites. The extraction of the free and conjugated metabolites was studied by liquid-solid procedures using styrene-divinylbenzene copolymers (Amberlite XAD-2) and bonded octadecyl silica supports (ODS-silica). Optimum recovery was obtained with ODS-silica extraction using 25% acetonitrile in a 5 mM diammonium phosphate buffer pH 2.1 as elution solvent. The chromatographic behaviour of naltrexone metabolites and naloxone (internal standard) was examined by varying the mobile phase composition. Increments of both the diammonium phosphate buffer concentration and the percentage of organic solvent in the eluent decreases the retention of compounds in a non-linear manner. Increments of the dodecyl sulphate (counter-ion) concentration, increases the retention time. The method was applied to determine the urinary levels of major naltrexone metabolites in a volunteer receiving a 50 mg oral dose. This is the first method reported which permits the simultaneous quantitative determination of naltrexone and its metabolites, 6beta-naltrexol, naltrexone glucuronide and 6beta-naltrexol glucuronide, in urine.

Journal Article↗
PubMed1988

Alcohol antagonism of hypercortisolism induced by naloxone.

The reversal of acute alcohol intoxication by naloxone is controversial. Naloxone increases cortisol secretion but there are no reports of this effect during acute alcohol intoxication. This study examines the effect of 20 mg naloxone on alcohol-induced intoxication using a balanced placebo design to investigate the role of cortisol, participant expectancy of treatment, and possible pharmacokinetic interactions during intoxication. Our results show differences in the time course of subjective self-evaluation of drunkenness in the presence of naloxone. Also, changes are observed in naloxone pharmacokinetic parameters with the ingestion of alcohol, specifically a decrease in plasma clearance. Whereas the cortisol response induced by naloxone was greater in the subgroup of participants with positive expectancy, in the presence of alcohol the naloxone effect on cortisol response was not observed. These observations may help explain the observed reversal of alcohol-induced coma by naloxone in a subgroup of patients.

Adult↗
PubMed1987

Accumulation of caffeine in healthy volunteers treated with furafylline.

The pharmacokinetics and tolerance of repeated oral doses of furafylline were investigated in normal volunteers. In accord with predictions from single dose studies, steady state was achieved on the first day following the administration of 90 mg and maintained by subsequent daily doses of 30 mg. When corrected for body weight there were no significant differences in minimum and maximum plateau levels of furafylline between males (1.2-2.0 micrograms ml-1; mean body weight 67.2 kg) and females (1.6-2.6 micrograms ml-1; mean body weight 54.9 kg). The half-life of elimination was less when the plasma concentration was lower than 600 ng ml-1 than during the stationary phase of treatment. Despite constant plasma levels the repeated administration of furafylline appeared to be associated with the onset of adverse xanthine-like side effects, a finding which was subsequently traced to the presence of, and possible synergism with, accumulating serum levels of caffeine in those volunteers drinking caffeine containing beverages. Subsequent studies showed that a single dose (90 mg) of furafylline results in a rapid accumulation of caffeine given orally (100 mg twice daily) and that this is accompanied by an elimination half-life of some 50 h and an abrupt decrease in metabolite levels. The furafylline-induced accumulation of caffeine was not influenced by the smoking habits of the subjects, implying that the metabolite pathway blocked by furafylline is the demethylation of caffeine in position 3, an implication confirmed by the reduced formation of paraxanthine. This demonstration of an unacceptable level of adverse side effects resulting from a potent inhibiting effect of furafylline on the metabolism of a normal dietary constituent has obvious implications in the interpretation of drug-induced toxicity.

Administration, Oral↗
PubMed1987

An animal model for the detection of drug-induced inhibition of caffeine metabolism.

Plasma levels of caffeine are increased more than 400% in rats given furafylline (10 mg kg-1 p.o.) and caffeine (25 mg kg-1 p.o.) as compared to rats given caffeine alone. In rats given idrocilamide (100 mg kg-1 p.o.) and caffeine (25 mg kg-1 p.o.) accumulation of xanthine is higher than 600%. The chromatographic separation and analysis of plasma extracts indicates that the N3-demethylation pathway is inhibited. Since furafylline and idrocilamide have been shown to increase blood levels of caffeine by the same mechanisms in humans and to give rise to adverse reactions, the rat would appear to be a suitable model to detect and study the inhibition of the metabolism of caffeine by such drugs and could be usefully included in the usual series of drug interaction studies done routinely during drug development.

Animals↗
PubMed1986

Some pharmacokinetic characteristics of furafylline, a new 1,3,8-trisubstituted xanthine.

After administration of furafylline, a, 1,3,8-trisubstituted xanthine, to beagle dogs at 0.5 and 10 mg kg-1 an elimination half-life 2-10 times longer than that of theophylline was observed. The kinetics were dose-dependent but no phase I metabolites were detected. When the compound was given orally to humans at a dose of 1.3-1.9 mg kg-1 a mean beta elimination half-life of 48.1 +/- 10.8 h was obtained after an initial distribution phase. Evidence of non-linear kinetics for plasma levels below 0.6 microgram ml-1 was also obtained. Other 1,3,8-trisubstituted xanthines, may also have a lower elimination rate than theophylline.

Adult↗
PubMed1985

Determination of heptaminol in plasma by thin-layer chromatography and in situ fluorimetry.

A method has been developed for the determination of heptaminol in plasma samples. The main steps involved in the assay are: ethereal extraction at an alkaline pH; concentration of the extracted heptaminol as its hydrochloride; formation of a fluorescent derivative by reaction with 4-chloro-7-nitrobenzo-2,1,3-oxadiazole; separation of the fluorophore by thin-layer chromatography and in situ quantitation of the emitted fluorescence by photodensitometry. The sensitivity limit is estimated to be 25 ng ml(-1) plasma, the overall recovery is 81% and the relative standard deviation is 6% at 200 ng ml(-1). The assay is useful in studies on the pharmacokinetics of heptaminol in animals or man after administration of therapeutic doses. Plasma levels of the drug following administration of 5 mg.kg(-1) to rats are reported.

Journal Article↗