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Biomedical subjects

A Durand

Publications and source records attributed to A Durand.

At least 127 records · Page 7Linked to original sources
PubMed1989

Lack of effect of spiramycin on cyclosporin pharmacokinetics.

1. The influence of spiramycin coadministration on cyclosporin pharmacokinetics was studied in five renal transplant patients. The plasma concentrations of cyclosporin were measured both by non-specific radioimmunoassay (RIA) and high-performance liquid chromatography (h.p.l.c.). 2. The kinetics of cyclosporin were followed before treatment, and after 1 day and then 2 weeks of oral treatment with spiramycin (3 X 10(6) iu, twice daily). The main pharmacokinetic parameters (the area under the plasma drug concentration-time curve, the maximum plasma drug concentration and the time to reach it) obtained both by RIA and h.p.l.c. were not modified by spiramycin cotreatment after 1 day, nor after 2 weeks of spiramycin administration. Therefore, the pharmacokinetics of cyclosporin (parent drug and parent drug plus metabolites) are not influenced by the coadministration of spiramycin macrolide at therapeutic dosage. 3. Spiramycin may be preferable to other macrolide antibiotics known to interact with cyclosporin such as erythromycin or josamycin.

Adolescent↗
PubMed1989

Effect of renal failure on the pharmacokinetics of ethyl loflazepate (Victan) in man.

The kinetics of ethyl loflazepate were studied in patients with various degrees of renal failure. A strong correlation was noted between urinary excretion of metabolite loflazepate and creatinine clearance. In contrast, elimination half-life and total plasma clearance of the sum of loflazepate + descarboxyloflazepate seemed to be independent of the degree of renal impairment. These results indicate the absence of a risk of accumulation of the 2 main and active metabolites of ethyl loflazepate in patients with renal failure.

Administration, Oral↗
PubMed1989

Determination of acitretin and 13-cis-acitretin in skin.

The aim of the study was to investigate the concentrations of Ro 10-1670 (acitretin) and its isomeric metabolite Ro 13-7652 (cis-acitretin) after multiple oral dosing of acitretin. We used a highly sensitive HPLC method for simultaneous determination of the 2 retinoids with a quantification limit of 2 ng/ml in plasma and 10 ng/g in total skin (epidermis and dermis). In hairless rats receiving orally 8 mg/kg acitretin once daily during 8 days, blood and skin samples were taken at different time points between 5 and 96 h after the last dose. After 96 h, appreciable concentrations of Ro 10-1670, but not Ro 13-7652 could be measured in the skin, whereas both isomers were below the quantification limit in plasma. In psoriatic patients treated with a once daily dose of 30 mg acitretin, blood samples and biopsies were taken after 1 month of treatment (i.e. under steady state conditions). 24 h after the last drug intake, skin concentrations of acitretin were approximately 10 times higher than those observed in plasma. Ro 10-1670 concentrations in the skin were approximately 3-5 times higher than for Ro 13-7652 and concentrations of both isomers were higher in lesional compared to uninvolved skin.

Acitretin↗
PubMed1989

Pharmacokinetics, brain distribution and pharmaco-electrocorticographic profile of zolpidem, a new hypnotic, in the rat.

Zolpidem [N,N-6-trimethyl-2-(4-methylphenyl)imidazo[1,2-a]pyridine-3- acetamide] administered as the hemitartrate salt has proven to be an effective hypnotic agent in animals and humans. This study describes the pharmacokinetic behavior of zolpidem in plasma and brain of rat after i.v. and p.o. administration of 2.63 mg.kg-1 of [14C]zolpidem (dose expressed as the base). Autoradiography was used to examine the regional distribution of the compound and the metabolic profile of zolpidem in the plasma and brain was also investigated. The pharmacokinetic data were related to electrocorticogram power spectral analysis. After i.v. administration, the disappearance of zolpidem from plasma fitted a biexponential model with a rapid phase of 0.2 to 0.3 hr and a slower phase of 1.3 to 1.5 hr. After p.o. dosing, peak plasma concentrations where already attained at 15 min (first sampling time). Independent of the route of administration, the concentrations of zolpidem in the brain at shorter times were 30 to 50% those of the plasma values. Furthermore, up to 1 hr, zolpidem accounted for 80 to 90% of brain radioactivity. The rate of disappearance from brain paralleled that from plasma. Autoradiographic studies confirmed the rapid absorption and elimination of zolpidem as well as the relatively homogenous distribution throughout the brain. Electrocorticogram analysis in immobilized rats after i.v. administration of zolpidem showed a rapid onset and a short-acting sedative effect compatible with the kinetic profile of the parent compound. Metabolites of zolpidem displayed a poor penetration into the brain and no significant hypnotic activity. At the dose of zolpidem used, no alteration of the sleep pattern was observed.

Animals↗
PubMed1988

Direct enantiomeric separation of betaxolol with applications to analysis of bulk drug and biological samples.

A direct method is described for the resolution of the enantiomers of betaxolol, a novel cardioselective beta-adrenergic blocking agent, using a tris(3,5-dimethylphenylcarbamate)cellulose chiral column. An excellent resolution of the two antipodes is obtained (Rs greater than 2) with high peak symmetries. The method is simple and ideally suited to the routine control of the enantiomeric excess in the bulk drug and the analysis of the enantiomers of betaxolol in hepatocyte suspensions. With modification of the polar modifier in a hexane-based mobile phase, most commercially available beta-blockers can be baseline resolved.

Adrenergic beta-Antagonists↗
PubMed1988

Comparative study of the pharmacokinetics of zuclopenthixol decanoate and fluphenazine decanoate.

Seventeen outpatients were treated with depot neuroleptics, zuclopenthixol decanoate in Viscoleo or fluphenazine decanoate in sesame oil, with dosage intervals of 3 weeks. During the 4th, 6th, and 8th dosage interval blood samples were drawn in oxalated tubes. Plasma concentrations of the active neuroleptic drugs, zuclopenthixol and fluphenazine, were determined by high performance liquid chromatography. The concentrations indicated some interindividual as well as intraindividual variations. For zuclopenthixol the maximum concentration was most often seen at day 7 after injection, whereas the kinetics of the fluphenazine concentrations was more variable. There was an indication of more fluctuation in the 4th dosage interval than in the 8th dosage interval, possibly due to the fact that steady state has not yet been achieved at the 4th dosage interval.

Adult↗
PubMed1988

Islet cell and insulin autoantibodies in subjects at high risk for development of type 1 (insulin-dependent) diabetes mellitus: the Lyon family study.

Genetic determination as well as prospective analysis of islet cell autoantibodies and autoantibodies to insulin were conducted in a population of 479 first degree relatives of 174 Type 1 (insulin-dependent) diabetic patients. Analysis of HLA haplotypes within families illustrated the high frequency of DR3 and DR4 alleles with preferential transmission from parent to both affected and unaffected offspring. DR4 was preferentially associated with DQw3.2 (TA10-) in 60/73 (82.2%) patients and 101/127 (79.5%) relatives. Relatives have been followed for a period of 800 subject-years. Twenty-two out of 430 relatives (5.1%) were found islet cell antibodies (ICA-IgG) positive. Seven sera with low titres became negative 6 months later at two different determinations. Fifteen sera ICA-IgG and ICA-protein A positive with high titres remained positive thereafter. Half of the ICA positive relatives were also found insulin autoantibodies (IAA) positive. All but 3 ICA negative relatives did not have IAA in their sera. Analysis of IAA specificity with competition experiments indicated that most antibodies recognised epitopes shared between human and pork insulins while four were specific for human insulin determinants. Analysis of class I and class II HLA antigen distribution indicated no particular allelic restriction in antibody positive individuals. Metabolic status of antibody positive relatives was determined with oral and intravenous charge of glucose. Two haplo-identical DR3-DQw2 brothers became diabetic during the study. One child and one mother both with DR4-DQw3.2 became intolerant to glucose. Each of these relatives had high titre ICA prior to metabolic deterioration.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1988

Inversely related evolution of growth hormone and prolactin secretions in long-term tissue cultures of human pituitary adenomas from acromegalic patients.

Pituitary tumoral tissue from 20 acromegalic patients was cultured for up to 120 d in a medium containing 5 nM cortisol. In all cultures, growth hormone (GH) release decreased. At the beginning of the culture, prolactin (PRL) was detected in 18 adenomas, varying from 0.5 to 1000 ng per flask per day. Thereafter, in 10 cases PRL secretion increased from 3 to 50 times the basal level, most frequently after a lapse of 9 to 30 d. PRL secretion remained low in three cases, undetectable in one case only. When added at 350 nM, cortisol increased GH secretion up to 20-fold and simultaneously decreased PRL secretion by as much as 10% of the basal level. Withdrawing cortisol reversed the situation. Immunocytochemical studies of the tumor at surgery showed, besides GH immunoreactive (IR) cells, PRL-IR cells (from rare cells to 10% of total cells) in 15 adenomas, correlating with the first days of culture PRL levels. In cultured explants, mitoses were never found. In 5 nM cortisol medium, the number of GH-IR cells decreased and PRL-IR cells increased or appeared. With 350 nM cortisol, the number of GH-IR cells increased, and PRL-IR cells were scarce or absent. Immunoreactivities for GH and PRL were found in different cells. Care was taken to exclude cultures containing normal pituitary tissue, and because no mitoses were found, these results suggest that most somatotropic adenomas can reversibly shift their secretion from GH to PRL in culture. This capacity to secrete PRL, hidden or low in vivo, is revealed by the favorable low cortisol conditions present in vitro.

Acromegaly↗
PubMed1988

Cellular immunity to Trypanosoma cruzi is mediated by helper T cells (CD4+).

The infection of mice with Trypanosoma cruzi has been used as an experimental model for human Chagas disease, because the murine and human infections have similar acute and chronic phases generating similar immunopathological phenomena. Histopathological studies of murine tissues showed that the inflammatory lesions were small during the acute phase and composed mainly of mononuclear cells. During the chronic phase, cellular infiltrates were clustered in large granulomata consisting of mononuclear and polynuclear neutrophil cells. Characterization of the infiltrating cells by surface markers showed that about 6% were Thyl.2+ T cells, and CD4+(Lyt 1+) T cells (T helper/DTH subset) were more numerous than CD8+(Lyt 2+) T cells. These observations suggest that delayed type hypersensitivity plays a role in the pathology of Chagas disease.

Animals↗
PubMed1988

Structure, function, and immunogenicity of human insulinoma cells.

Dissociated human insulinoma cells were plated onto plastic multiwell dishes. Cells were maintained for 1 mo on plastic with three passages. Cultures consisted of small colonies with some areas of stratification and few intercellular spaces. Ultrastructural studies indicated that cultured cells had epithelial features with desmosomes at cell-to-cell contacts and intermediate filaments in addition to secretory granules in the cytoplasm. Insulin and C-peptide were released in equimolar amounts in culture media. When challenged for 30 min with 16.7 mM glucose, 1 mM 3-isobutyl-1-methylxanthine, 4 mM tolbutamide, or 10(-6) M glucagon, insulinoma cells responded by a 1.5-, 1.5-, 2-, or 3-fold increase, respectively, in insulin release above baseline levels. A 15-min challenge with 10(-5) M isoproterenol increased insulin secretion by 1.85-fold. By indirect immunofluorescence, an anti-insulin antibody reacted positively with cell cytoplasm, whereas anti-somatostatin and anti-glucagon antibodies did not. Insulinoma cell surface expressed class I MHC molecules but not class II molecules. Immediately after isolation, crude insulinoma cells were contaminated by 2% of DR+ cells from nonislet components that disappeared after several weeks in culture. The ability of insulinoma cells to stimulate allogenic T-lymphocyte proliferation was assessed by [3H]thymidine incorporation in mixed culture combinations. Crude insulinoma cells elicited a strong lymphoproliferative response with a stimulation index ranging between 3.5 and 7, whereas no stimulation was found after 1 mo in culture. It is postulated that absence of class II-positive cells in the stimulatory cell preparation conditioned this immune tolerance across the major histocompatibility barrier.(ABSTRACT TRUNCATED AT 250 WORDS)

1-Methyl-3-isobutylxanthine↗
PubMed1988

New approach in bioavailability study of two formulations of ethyl loflazepate.

The disposition of ethyl loflazepate (Victan) was studied on 12 healthy male volunteers after administration of the two oral formulations of the drug: one 4-mg tablet and two 2-mg tablets according to an open crossover single dose comparison. A model-independent analysis and a model-dependent approach were used to treat experimental data. Appropriate statistical tests (ANOVA, Wilcoxon test, Westlake test for model-independent parameters; principal components analysis, Hotelling T2 test for model-dependent parameters) demonstrated the bioequivalence of the two formulations.

Administration, Oral↗
PubMed1988

Residual plasma concentrations of acitretin (Ro 10-1670) and its metabolite (Ro 13-7652) after chronic administration.

In order to study the elimination of Ro 10-1670 (acitretin) and Ro 13-7652, its 13-cis-isomeric metabolite after chronic administration, determination of the residual plasma concentrations of these two compounds were assayed in 9 patients in a range of 22-30 days following cessation of a 2- to 7.5-month course with daily oral doses of 10-50 mg of acitretin. A highly sensitive HPLC method was used (2 ng/ml). Residual plasma concentrations of Ro 10-1670 were below the quantification limit in all cases. Residual plasma concentrations of Ro 13-7652 were below the quantification limit in 7 cases and respectively of 3 and 4 ng/ml in the other 2 cases. These data appear to confirm the absence of storage of acitretin even after an extended course of therapy.

Acitretin↗
PubMed1987

Citalopram--a highly selective 5-HT uptake inhibitor--in the treatment of depressed patients.

In an open, clinical trial comprising a total of 21 depressed in-patients (6 men and 15 women) citalopram was administered in doses of 20-60 mg once daily for a period of at least 3 weeks. Fourteen of the patients were treated for 4 weeks, and 6 of these patients were treated for another 2 weeks. The CPRS subscale for depression (MADRS) and a global evaluation were used for assessment of the therapeutic effect. Twelve patients showed complete or partial response to treatment, and generally onset of therapeutic effect was seen within the first 2 weeks of treatment. Side-effects were generally few and mild, anxiety being the most frequent one. No pathological laboratory values were recorded, and apart from one case of slight and transient bradycardia no changes were observed in the cardiovascular parameters. Determination of plasma levels in 16 of the patients under presumed steady-state conditions showed an inter-individual variation between 28 and 616 nM/l for citalopram and between 32 and 338 nM/l for its monodemethylated metabolite for daily citalopram doses of 30-60 mg. The average ratio citalopram-desmethyl citalopram was 1.70. No correlation was found between clinical response and the plasma levels.

Adult↗
PubMed1987

Human islet cell autoantibodies specifically bind cloned rat islet cells.

Sera from newly diagnosed type I (insulin dependent) diabetic patients and control subjects were tested by indirect immunofluorescence on a particular subclone of RINm5F cells for the presence of cytoplasmic antibodies. Cell cultures after biochemical fixation and frozen sections of cell sheets obtained after incubating confluent monolayers with dispase were used alternatively as substrate. Eight out of ten ICA positive sera previously tested on frozen sections of human pancreas bind RIN cells when fixed with acetone-ethanol whereas no staining was obtained after treating the cells with paraformaldehyde or glutaraldehyde. Four normal sera did not bind RIN cells under these conditions. Alternatively, frozen sections of cell sheets appeared to be a more sensitive substrate as all ICA positive sera tested reacted with cell cytoplasm. In addition, an immunoradiometric assay was developed using microtitre plate wells coated with Nonidet P40 solubilized RIN antigens. Coated wells were incubated with ICA positive and ICA negative diabetic sera along with sera from normal individuals. Antigen antibody complexes were detected by the binding of 125I-Protein A. A good correlation was found between binding values and results obtained by indirect immunofluorescence on frozen sections of human pancreas. Although this study indicates that RIN cells express a specific cytoplasmic antigen to which ICA positive sera bind, more information is required concerning the exact nature of this antigen before such assay can be reliably used for the detection of ICA.

Animals↗