L Balant

University of Geneva, Genève, Geneva, Switzerland

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Publications (111)256.03 Total impact

  • Journal of Clinical Pharmacy and Therapeutics 06/2008; 4(2):87 - 93. · 2.10 Impact Factor
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    ABSTRACT: Digoxin serum levels are measured after intravenous infusion of a 2 mg dose. The pharmacokinetic parameters for a two and three-compartment open-body model are calculated by compartmental analysis using a digital computer; the three-compartment open-body model gives the superior fit.The behaviour of digoxin during multiple administration is predicted and compared to the experimental results obtained after eleven intravenous injections of 0·5 mg digoxin.For pharmacokinetic and pharmacodynamic purposes the behaviour of digoxin in man is best described by a three-compartment open body model. For clinical purposes, such as determining the optimum dosage regimen for individual patients, a simpler moder might be adequate and easier to use.
    Journal of Clinical Pharmacy and Therapeutics 06/2008; 5(1):35 - 42. · 2.10 Impact Factor
  • L. Balant, C. A. Hunt
    Journal of Clinical Pharmacy and Therapeutics 06/2008; 5(1):31 - 34. · 2.10 Impact Factor
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    ABSTRACT: The objective of this work was to investigate the interactions of poly(D,L-lactic acid) nanoparticles prepared by a recently developed salting-out process, with lymphocytes and monocytes isolated from healthy human donors. Nanoparticles were labeled with a hydrophobic fluorescent dye and incubated with lymphocytes and monocytes, and their uptake was followed by flow cytometry in the presence and absence of plasma. Plasma protein adsorption increased nanoparticle uptake by monocytes, whereas a decrease of cellular binding of the nanoparticles to lymphocytes was noted. The cellular uptake for both cell types consisted in a passive adsorption and in an energy requiring process, because the cells became 2–3 times more fluorescent when the incubation temperature was increased from 4 to 37°C. When nanoparticles were coated with polyethylene glycol 20,000, uptake by monocytes decreased by 43 and 78% in phosphatebuffered saline and plasma, respectively; a similar decrease in nanoparticle uptake was observed for lymphocytes. Two-dimensional gel electrophoresis was performed to identify the plasma opsonins adsorbed onto the nanoparticle surface. Protein mappings for uncoated and polyethylene glycol-coated nanoparticles differed for two spot series. These spots, not yet clearly identified, may represent specific apolipoproteins involved in the metabolism of human lipoproteins, indicating the possible involvement of specific receptors in the uptake of the nanoparticles. © 1994 John Wiley & Sons, Inc.
    Journal of Biomedical Materials Research 09/2004; 28(4):471 - 481.
  • Source
    Malcolm Rowland, Luc Balant, Carl Peck
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    ABSTRACT: A 2-day workshop on "Physiologically Based Pharmacokinetics (PBPK) in Drug Development and Regulatory Science" came to a successful conclusion on May 30, 2002, in Washington, DC. More than 120 international participants from the environmental and predominantly pharmaceutical industries, Food and Drug Administration (FDA), and universities attended this workshop, organized by the Center for Drug Development Science, Georgetown University, Washington, DC. The first of its kind specifically devoted to the subject, this intensive workshop, comprising 7 plenary presentations and 10 breakout sessions addressed 2 major objectives: (1) to "define demonstrated and potential contributions of PBPK in drug development and regulatory science," and (2) to "assess current PBPK methodologies with the identification of their limitations and outstanding issues." This report summarizes the presentations and recommendations that emerged from the workshop, while providing key references, software, and PBPK data sources in the appendices. The first day was initially devoted to presentations setting the stage and providing demonstrated applications to date. This was followed by breakout sessions that considered further opportunities and limitations, and which extended into Day 2 to deal with developments in methodologies and tools. Although the primary emphasis was on pharmacokinetics, consideration was also given to its integration specifically with mechanism-based pharmacodynamics.
    The AAPS Journal 02/2004; 6(1):56-67. · 4.39 Impact Factor
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    ABSTRACT: Saliva was tested and evaluated as a biological matrix for methadone (Mtd) monitoring. Conventional method using a narrow bore C18 column, and an enantioselective method using a narrow bore alpha1-acid glycoprotein column, were developed using liquid chromatography coupled with a mass spectromeric (MS) detector. After optimisation of MS conditions by flow injection analysis, selected ion monitoring detection was used to enhance sensitivity. The total Mtd concentration and the enantiomeric ratio in saliva were validated using an experimental design. The methods were applied to samples provided by heroin addicts undergoing a Mtd treatment. Results on total Mtd determination showed a very poor correlation between saliva and serum, whereas the enantiomeric ratios of Mtd gave a very good one.
    Journal of Chromatography A 03/2000; 871(1-2):163-72. · 4.61 Impact Factor
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    ABSTRACT: A stereoselective analysis of methadone (Mtd) in whole blood and serum was developed using liquid chromatography on a protein based chiral stationary phase. Liquid-liquid extraction (LLE) and solid phase extraction methods were applied before chromatographic analysis. The extraction procedure, as well as the choice of the biological matrix, showed significant differences in the extraction yield and in the precision of the assays. Serum was selected for this assay and LLE was chosen as the preparation step because of its simplicity and rapidity. The total procedure was validated and applied to clinical samples. Samples taken from 45 heroin-addicted patients were analyzed. A correlation was found between the dose administered and Mtd concentration (total and R-form), but interindividual variability of the total normalized Mtd was seen (concentration varied from 90 to 530 ng/ml). Furthermore, two populations were apparently observed with a mean Mtd concentration of 200 and 475 ng/ml, respectively. Stereoselective analyses showed that more than 50% of the patients presented a nonracemic ratio, and particularly about 25% showed a preferential metabolism of the active R-Mtd enantiomer. Therefore, the stereoselective determination of Mtd is necessary to improve the quality of the treatment of heroin addiction.
    Chirality 02/1999; 11(5-6):487-94. · 1.72 Impact Factor
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    ABSTRACT: The purpose of this study was to evaluate the possible advantages of floating and high-density dosage forms and their influence on pharmacokinetic parameters. Atenolol was chosen as a model drug because of its poor absorption in the lower gastrointestinal tract. Three formulations containing 25 mg atenolol, a floating multiple-unit capsule, a high-density multiple-unit capsule, and an immediate-release tablet were compared with respect to estimated pharmacokinetic parameters. The two multiple-unit dosage forms were composed of compressed minitablets and had sustained release properties. The bioavailability of the two gastroretentive preparations with sustained release characteristics was significantly decreased when compared to the immediate-release tablet. The floating minitablets seemed to be retained longer in the stomach than the high-density dosage form. The first atenolol concentration detectable in the plasma and the time to peak Tmax were delayed for the floating dosage form. For the parameters Cmax and AUC 0-infinity, the lower limit of the 90% confidence interval was outside the bioequivalence range (0.80-1.25). This study showed that it was not possible to increase the bioavailability of a poorly absorbed drug such as atenolol using gastroretentive formulations. Atenolol absorption was delayed and the maximum plasma concentration was diminished.
    Pharmaceutica Acta Helvetiae 08/1998; 73(2):81-7.
  • Process Biochemistry 01/1998; 33(1). · 2.44 Impact Factor
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    ABSTRACT: After intravenous administration, nanoparticles suffer a major drawback in that they are rapidly and massively taken up by the cells of the mononuclear phagocyte system. The mechanisms involved in the opsonization, adhesion, and internalization of biodegradable nanoparticles by the mononuclear phagocyte system are still poorly understood. In this work, the kinetics of blood protein adsorption onto nanoparticles of poly(D,L-lactic acid) prepared by the salting-out technique was investigated. Nanoparticles of 312 nm were incubated for variable periods of time (5-60 min) in human serum and citrated plasma. After incubation, the particles were washed and the proteins detached from them, denatured, and analyzed by two-dimensional polyacrylamide gel electrophoresis. In plasma, the predominant protein was immunoglobulin G (IgG), and the amount adsorbed was not dependent on incubation time. Albumin amounts were high for short incubation periods but decreased as a function of time, whereas apolipoprotein E levels increased significantly as a function of the incubation period. Owing to the possible complement cascade inactivation by addition of citrate to plasma, the kinetics of adsorption was also evaluated in serum. In this medium, adsorption of complement C3 components onto the surface of the nanoparticles was clearly evidenced by spots of increasing intensity and area, reaching levels comparable to those of the omnipresent IgG. This result confirms the important role of complement components in the opsonization process of poly(D,L-lactic acid) particles.
    Journal of Biomedical Materials Research 12/1997; 37(2):229-34.
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    ABSTRACT: The aim of this study was to quantitate the density of guanine nucleotide-binding (G) protein subunits (inhibitory G alpha i, stimulatory G alpha s, G alpha q/11, and G beta) in platelets of unipolar depressed patients to assess the status of these signal transduction proteins in depression and the effects of antidepressant drug treatment. Blood platelets were collected from 22 drug-free depressed patients and 22 age- and sex-matched healthy controls. The levels of the various G protein subunits were assessed by immunoblotting techniques. The immunoreactivity of G alpha 12 was increased (41%) and that of G alpha i3 decreased (25%) in platelets of depressed patients. The levels of other G protein subunits (G alpha s, G alpha q/11, G beta) did not change significantly with respect to those of control subjects. Chronic administration of cyclic antidepressant drugs (citalopram, clomipramine, imipramine) decreased the immunoreactivity of the up-regulated G alpha i2 protein (31%). Since platelet G alpha i2 is in line with the existence of supersensitivity of these receptors in major depression.
    Biological Psychiatry 11/1997; 42(8):704-12. · 9.25 Impact Factor
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    ABSTRACT: The objective of the present study was to determine the basis for dosing time-dependent changes in the ocular and systemic absorption of topically applied timolol in pigmented rabbits. The gamma scintigraphic technique was used to monitor the changes in precorneal solution retention following instillation. Changes in timolol concentration in the plasma over 120 min and in various anterior segment eye tissues at 30 min following the topical instillation of 25 microliters of 0.65% timolol maleate solutions at various dosing times were monitored using reversed phase HPLC. Corneal and conjunctival permeability at various dosing times was evaluated in the modified Ussing chamber. The results indicated that precorneal solution drainage was slowest at noon. Suppressing tear production by anesthesia led to an increase in ocular timolol absorption at 6 a.m. but not at other dosing times, in spite of the lowest corneal permeability then. There was no statistically significant dosing time influence on systemic timolol absorption following nasal or conjunctival dosing. In conclusion, possible diurnal changes in precorneal solution clearance may be the main factor underlying the diurnal changes in ocular as well as systemic timolol absorption in rabbits. In addition, diurnal changes in corneal permeability may also contribute to diurnal changes in ocular timolol absorption.
    Journal of Ocular Pharmacology and Therapeutics 02/1996; 12(2):103-13. · 1.29 Impact Factor
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    ABSTRACT: Glycoprotein modifications in the glycan moiety can occur in diseases such as cancers, inflammatory processes and alcoholism. We combined high-resolution two-dimensional polyacrylamide gel electrophoresis (2-D PAGE) with lectin affinoblotting in order to establish the normal human plasma glycoprotein map. Human plasma proteins were separated by mini 2-D PAGE (7 x 9 cm), transferred onto polyvinylidene difluoride membranes and incubated with biotinylated lectins. We focused our study on lectins binding sialic acid and galactose residues. Known plasma glycoproteins such as alpha 1-antitrypsin, alpha 1-antichymotrypsin, alpha 2-HS glycoprotein, alpha 1-acid glycoprotein, haptoglobin beta-chain and transferrin were easily detected in ng amounts. This protocol was adequate to establish a normal plasma glycoprotein map and will allow the study of glycoproteins in diseases.
    Electrophoresis 08/1995; 16(7):1187-9. · 3.26 Impact Factor
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    ABSTRACT: Self reports of flushing reaction after drinking, cutaneous sensitivity to alcohol (patch test), and genotypic determination of ADH2, ADH3, and ALDH2 were studied in 53 Brazilian volunteers of different ethnic groups. Genotypes were determined using single-strand conformation polymorphism in discontinuous buffer electrophoresis. Analysis of the results indicated several cases of a reported flushing reaction among ALDH2 1/1 individuals, while all but 2 cases of ALDH2 heterozygotes reported a flushing reaction. The latter subjects also had a negative result in the patch test. These preliminary results indicate that variability in the facial flushing reaction to alcohol seems to be a phenomenon resulting not only from the presence of a deficient ALDH2*2 allele, but also from other polymorphisms of alcohol-metabolizing enzymes.
    Brazilian Journal of Medical and Biological Research 06/1995; 28(5):513-8. · 1.14 Impact Factor
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    ABSTRACT: The influence of genetic variation in alcohol dehydrogenase (ADH; EC 1.1.1.1) and aldehyde dehydrogenase (ALDH; EC 1.2.1.3) on the metabolic pattern of serotonin (5-hydroxytryptamine, 5-HT) in humans was examined from the relative urinary concentrations of the end products 5-hydroxyindole-3-acetic acid (5-HIAA) and 5-hydroxytryptophol (5-HTOL). Healthy Caucasian (Swedish) and Oriental (Chinese) subjects were genotyped for ADH2, ADH3 and ALDH2 by a PCR/SSCP technique. The 5-HTOL/5-HIAA ratios ranged between 0.9-9.4 pmol/nmol (4.4 +/- 1.8, mean +/- SD, n = 143). No significant difference in the 5-HT metabolic pattern was observed between Caucasians and Orientals (4.3 +/- 1.8 and 4.4 +/- 1.8 pmol/nmol, respectively), nor between any of the ADH2, ADH3 and ALDH2 genotypes. Despite the modulatory effects of genetic variation of these enzymes on ethanol metabolism, the present results indicate that the individual isozyme composition of ADH2, ADH3 and ALDH2 is not important for the metabolic pattern of 5-HT.
    Life Sciences 02/1994; 55(5):359-66. · 2.56 Impact Factor
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    ABSTRACT: Under appropriate conditions single strand conformation polymorphism (SSCP) analysis of polymerase chain reaction (PCR) products allows the detection of single base mutations in a given DNA fragment. We adapted this method for the routine determination of allele variants of human alcohol and acetaldehyde dehydrogenase without radioisotopic labeling. After PCR amplification of the selected exon, the DNA fragments were heat-denatured and loaded on a polyacrylamide gel containing glycerol. For electrophoresis a discontinuous buffer system was used with sulfate as leading ion and borate as trailing ion. The DNA bands were revealed by silver staining. Acrylamide concentrations, ionic strength and electrophoresis temperature were systematically investigated for each DNA fragment. The polymorphisms detected by SSCP were identical to those found by hybridization with 32P-labeled allele-specific oligonucleotides. This method avoids the use of radioactivity, is less expensive and simpler than the allele-specific oligonucleotide (ASO) methodology and thus particularly suited for routine analysis.
    Electrophoresis 08/1993; 14(7):566-9. · 3.26 Impact Factor
  • J Fabre, J P Assal, L Balant, P Dayer
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    ABSTRACT: Approximately one half of the patients takes prescribed medications irregularly or omits these altogether. On the basis of our own observations and published reports we analyze the factors influencing compliance. The motivation of the patients plays a decisive role, it is rooted in the meaning the patient gives to his existence, to where the strength of his family bonds and the confidence in the care-taking persons lays as well as the possibility to express himself which is most important. The better guidance and training of the doctors in the difficult task of strengthening such motivation may contribute to substantially improve this situation.
    Schweizerische Rundschau fur Medizin Praxis = Revue suisse de medecine Praxis 03/1992; 81(6):129-32.
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    ABSTRACT: The aim of this study was (a) to establish a red blood cell (RBC) protein map with immobilized pH gradient for the first dimension (b) to compare the pattern with previously published RBC protein map obtained with carrier-ampholyte pH gradients and (c) to localize four new enzymes on the map (i.e. 6-phosphogluconic dehydrogenase, glyceraldehyde-3-phosphate dehydrogenase, glutathione peroxidase and superoxide dismutase). This publication provides the most updated RBC polypeptide pattern with twelve proteins or enzymes localized on the map.
    Applied and theoretical electrophoresis: the official journal of the International Electrophoresis Society 02/1992; 3(2):77-82.
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    ABSTRACT: Examined the feasibility and accuracy of the Brief Psychiatric Rating Scale (BPRS) as an evaluative tool. 80 psychiatric inpatients (aged 17–63 yrs) were evaluated with the BPRS on the day of admission and every subsequent 10th day. Results indicate that the BPRS shows a factor structure that is consistent with previous studies (e.g., J. E. Overall; 1974). The BPRS represents a level of abstraction that is compatible with the way clinicians think and communicate about manifest psychopathology. Finally, the BPRS is sensitive to changes in the patient's condition during pharmacological treatment. (PsycINFO Database Record (c) 2012 APA, all rights reserved)
    European Psychiatry 01/1991; · 3.29 Impact Factor
  • Revue medicale de la Suisse romande 01/1988; 107(12):1007-12.

Publication Stats

991 Citations
256.03 Total Impact Points

Institutions

  • 1970–2008
    • University of Geneva
      • • Department of Psychiatry
      • • Department of Rehabilitation and Geriatrics
      • • Department of Biochemistry
      Genève, Geneva, Switzerland
  • 1994
    • Karolinska Institutet
      • Institutionen för klinisk neurovetenskap
      Solna, Stockholm, Sweden
  • 1980–1981
    • Policlinique Médicale Universitaire Lausanne
      Lausanne, Vaud, Switzerland