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Biomedical subjects

J Segura

Publications and source records attributed to J Segura.

At least 181 records · Page 10Linked to original sources
PubMed1984

Serum levels of aluminium and magnesium in animals and man after administration of high doses of almagate.

Repeated administration of almagate (hydrated aluminium-magnesium hydroxycarbonate, Al2Mg6(OH)14(CO3)2 X 4 H2O, Almax) in doses up to 4 g/kg to rats for 30 days did not result in increased serum levels of magnesium. After single doses of 4 g/kg of almagate, aluminium could not be detected at the limit of detection (0.025 ppm). A slight but physiologically not significant increase in the concentrations of both of these ions was observed after administration of 0.27 g/kg to dogs but not after 0.135 g/kg. The absorption of aluminium and magnesium in volunteers treated for 5 days with almagate and two other non-systemic antacids was compared. There was no increment in the serum levels of magnesium above the basal level or of aluminium above the lowest detectable level. Almagate may therefore be classified as a non-systemic antacid.

Adult↗
PubMed1981

Human metabolism of 7-substituted theophyllines: N3-demethylation and lack of oxidation of proxyphylline.

Proxyphylline metabolism after oral administration to humans was studied. The only metabolic process detected was N3-demethylation, and 1-methyl-7-(2-hydroxypropyl)xanthine was isolated and identified. Proxyphylline was excreted in urine both an unchanged compound (12.7% of dose) and as its metabolic product (30.2% of dose). The latter substance was not found (detection limit = 1 microgram/ml) in the systemic circulation. Thus, it probably does not participate in the pharmacological activity of proxyphylline in vivo, although it was as active as the parent drug in relaxing the guinea pig tracheal chain. Lack of metabolism to uric acid derivatives is explained by the low affinity of both substances toward the enzymes the oxidize xanthine (xanthine oxidase) and methylxanthine derivatives. The presence of the metabolite in urine interferes with some analytical methods developed for estimation of unchanged proxyphylline. Published data on the urinary excretion of this drug need reevaluation.

Aminophylline↗
PubMed1981

The pharmacokinetics of a new benzamide drug clebopride, in the rat and the dog.

After intravenous, intramuscular and oral administration of clebopride in the rat and the dog its apparent volume of distribution is high (1.6-3.2 1 kg-1) and it has a longer biological half-life than metoclopramide in both species. High clearance values and concentrations of metabolites in plasma after oral administration indicate that the drug is subjected to an extensive first pass metabolism in the rat. Thus, clebopride administered orally gives relatively low concentrations in the systemic circulation in rats even though it is rapidly absorbed. The metabolic processes appear to become saturated at high doses which is reflected in dose-dependent kinetics. Linear kinetics were observed in the dog, although enterohepatic recycling could occur.

Animals↗
PubMed1980

Metabolism of clebopride in vitro. Mass spectrometry and identification of products of amide hydrolysis and N-debenzylation.

1. Electron impact and field desorption mass spectrometry is described and discussed for clebopride, a newly developed benzamide with anti-emetic and anti-dopaminergic properties, and for some related compounds. 2. When clebopride was incubated with liver homogenates of rabbits, 4-amino-5-chloro-2-methoxybenzoic acid and N-(4'-piperidyl)-4-amino-5-chloro-2-methoxybenzamide were identified as metabolites.

Animals↗
PubMed1979

Rapid thin-layer chromatographic photodensitometric method for the determination of metoclopramide and clebopride in the presence of some of their metabolic products.

Metoclopramide and its newly developed analogue clebopride, together with some of their metabolic products are quantitated, following extraction from biological tissues and fluids, and subsequent separation on silica gel thin-layer chromatographic plates. Diazotisation, followed by coupling with N-(1-naphthyl)ethylenediammonium dichloride, carried out on the thin-layer plate, is utilised for visualisation. The intensity of the spots is measured by photodensitometric analysis. The effect of variation of various experimental conditions is studied. The method has proven to be satisfactory for the measurement of 20 ng/ml of these compounds in biological material; the results are well within the accepted limits of deviation.

Animals↗
PubMed1979

Penetration of antibiotic into interstitial tissue fluid following parenteral administration of lysine cephalexin.

Serum and interstitial fluid levels of antibiotic have been measured at various times following i.m. administration of equivalent doses of lysine cephalexin and sodium ampicillin, in a cross-over design, to dogs fitted with s.c. implanted silastic "tissue cages" and the results subjected to pharmacokinetic analysis. Serum concentrations of cephalexin were consistently higher than those of ampicillin and elimination half-lives were calculated as 1.73 h and 0.87 h, respectively. The rate of appearance of cephalexin in the interstitial fluid (Ka 1.741 h-1 was faster than that for ampicillin (Ka 0.946 h-1) and the maximum concentration obtained also proved to be higher. The half-life of cephalexin in the interstitial fluid (6.79 h) was almost four times longer than that in serum whereas that of ampicillin (2.03 h) was only a little more than twice as long. As a consequence a greater concentration and retention in interstitial fluid was obtained with cephalexin at all times tested. Since the interstitial fluid levels of cephalexin were still relatively high 8-12 h after the administration of a single dose repeated administration of lysine cephalexin 2 or 3 times daily is expected to result in a beneficial accumulation of cephalexin in the interstitial fluid.

Ampicillin↗
PubMed1977

Intrahepatic vascular division in the pig: basis for partial hepatectomies.

Transplantation of resected hepatic fragments, with the attendant vascular and biliary tract reconstruction, presents difficulties. We have studied the intraparenchymal vascular division in the pig with a view to performing partial hepatectomies with the greastest possible anatomical support. Forty-six molds of the various vascular territories were obtained from the 31 porcine livers. Each segment of the median lobe is dependent on the adjacent lateral lobe. Its intersegmental fissure is the obligatory site for parenchymal section to be continued through horizontal portion of portal vein, hepatic artery, and left hepatic duct. A right hemihepatectomy unfailingly results in the devitalization of the left side of the liver. If the goal of a hepatectomy is the transplantation of the resected fragment, it is recommended that the right side of the liver be utilized, as its more convenient extrahepatic vascular and biliary calibre will permit pedicular conservation and anastomosis.

Animals↗
PubMed1976

Adsorption of tryptophan metabolites from physiological fluids on XAD-2 and determination by single ion monitoring.

Endogenous tryptamine, 5-hydroxytryptamine, indoleacetic acid, 5-hydroxyindoleacetic and tryptophan have been recovered from urine and cerebro-spinal fluid by adsorption on XAD-2 resin (0.3 g). After adsorption of the sample on the resin, desorption with methanol provides a single fraction that contains all of these metabolites. The mass spectra of their pentafluoropropionyl derivatives show prominent ions at m/e 276 and 438 which are characteristic of indoles and 5-hydroxyindoles, respectively, a feature that allows the concurrent determination of all the components of each group by functional group analysis. A method has been developed to carry out single ion monitoring with the peak matching system of an Hitachi RMU-6H mass spectrometer. Identifications are based on the respective Kovats Indices and single ion monitoring of two characteristic ions per compound: tryptophan (m/e 276 and 347); tryptamine (m/e 276 and 289); indoleacetic acid (m/e 276 and 335); 5-hydroxytryptamine (m/e 438 and 451); 5-hydroxyindoleacetic acid (m/e 438 and 497). The method described illustrates the feasibility of assaying biogenic indoleamines and acidic metabolites, as well as their precursor amino acid on a single fraction in contrast to other standard fractionation methods. This is possible even if the mass spectrometer is not equipped with an alternating voltage accelerator provided that it has a peak matcher, although the lack of an alternating voltage accelerator requires two separate injections of the same sample, for quantification and identification; one for the indole profile and another for the 5-hydroxyindole profile. Both profiles can be verified by individual monitoring of the other confirmatory ions. With this method the use of a multiple ion detector would allow a simultaneous determination of all of these metabolites in one gas chromatograph mass spectrometer run.

Adsorption↗
PubMed1976

The absorption and elimination of metoclopramide in three animal species.

The absorption and elimination of metoclopramide have been studied in the rat, rabbit and dog. Thin-layer chromatography followed by photodensitometry was used for the analysis of the unchanged drug and its metabolites. N-De-ethylation is an important Phase I metabolic reaction and conjugation with glucoronic acid and sulphate is a major route of metabolism, particularly in the rabbit. The pharmacokinetic parameters after intravenous administration showed little interspecies variation. First order elimination kinetics with short half-lives and high apparent volumes of distribution (greater than 1.1 kg(-1)) were observed. Major interspecies variations were seen after oral administration of high doses of the drug. Metoclopramide was eliminated slowly after oral administration to rats. The findings in the rabbit and in the dog suggest that the liver plays an active role reducing the systemic availability of unchanged metoclopramide after oral administration.

Animals↗
PubMed1976

Pharmacokinetics of sulpiride after oral and intravenous administration in the rat and the dog.

The plasma concentration of sulpiride was measured in the rat and in the dog after oral and i.v. administration of the drug. In the rat only traces (less than 1 mug/ml) of sulpiride were detected in plasma after an oral dose of 100 mg/kg. The peak concentrations in 3 dogs given 25, 50 or 100 mg/kg orally were 6.1, 15.6 and 23.9 mug/ml, respectively. The pharmacokinetic data after i.v. injection were compared to earlier observations with the related orthopramide compound, metoclopramide. The half-life of sulpiride in dog plasma (1.6 -- 3.4 hr) is longer than that of metoclopramide, but in the rat there is little difference between the two compounds. Both of the compounds have large total apparent volumes of distribution (1-2 1/kg) in the two species. The marked species difference in the systemic bioavailability of oral sulpiride should be taken into account when the orthopramide drugs are evaluated in pharmacological tests.

Administration, Oral↗