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1.
Pathol Biol (Paris) ; 52(10): 597-601, 2004 Dec.
Article in French | MEDLINE | ID: mdl-15596309

ABSTRACT

The interpretation of PK/PD indices is specific to each class of antibiotics. In order to illustrate this, we developed a multidisciplinary tutorial program based on simulation of clinical cases. Three drugs were included in this software: tobramycin, vancomycin and azithromycin. From the dosage regimen proposed by the user, the model simulates a plotting of antibiotic plasma concentrations vs. time (tobramycin, vancomycin and azithromycin) and tissue concentrations (azithromycin). Peak and trough concentrations are calculated at steady-state. A commentary is provided to evaluate the efficacy of treatment and to assist the user in improving his prescription of tobramycin or vancomycin. T(> MIC) (time the concentration remains above the MIC) and AUC(24) (area under the concentration-time curve) are calculated in plasma and tissues for azithromycin. In order to create a link between theoretical pharmacokinetics and clinical practice, we propose this model as a simulation of antibiotic monitoring. We put the emphasis on interactivity and simulation, leading to applied reasoning and decision making. It illustrates (i) the influence of pharmacokinetic parameters, location of infection and bactericidal kinetics on the use of three different classes of antibiotics, (ii) the role of route of administration, dosing and intervals between administrations on therapeutic response and (iii) the influence of erratic administrations on clinical efficacy.


Subject(s)
Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/pharmacokinetics , Computer Simulation , Anti-Bacterial Agents/classification , Anti-Bacterial Agents/therapeutic use , Area Under Curve , Azithromycin/blood , Humans , Infections/drug therapy , Microbial Sensitivity Tests , Tobramycin/blood , Vancomycin/blood
2.
J Chromatogr B Biomed Sci Appl ; 727(1-2): 235-9, 1999 Apr 30.
Article in English | MEDLINE | ID: mdl-10360443

ABSTRACT

A new liquid-liquid extraction is described for thiopurine methyl transferase (TPMT, EC 2.1.1.67) activity determination: the use of a pH 9.5 NH4Cl buffer solution, before adding the solvent mixture, allows more rapid extraction, avoiding a centrifugation step, and reduces the global cost of analysis. After the extraction step, 6-methylmercaptopurine, synthesised during the enzymatic reaction, is determined by a liquid chromatographic assay. Analytical performance of the assay was tested on spiked erythrocyte lysates. The linear concentration range was 5-250 ng ml(-1) (r> or =0.997, slope=1.497, intercept=-0.367). The recoveries were 82.8, 89.9 and 82.2% for 75, 125 and 225 ng ml(-1), respectively. The coefficients of variation were < or =6.1% for within-day assay (n=6) and < or =9.5% for between-day assay precision (n=6; 14 days). TPMT activity was determined in a French adult Caucasian population (7 =70). The results ranged from 7.8 to 27.8 nmol h(-1) ml(-1) packed red blood cells and the frequency distribution histogram is similar to that previously published.


Subject(s)
Chromatography, High Pressure Liquid/methods , Methyltransferases/blood , Adult , Erythrocytes/enzymology , Humans , Reproducibility of Results , Sensitivity and Specificity , Spectrophotometry, Ultraviolet
3.
J Pharm Biomed Anal ; 17(3): 481-5, 1998 Jul.
Article in English | MEDLINE | ID: mdl-9656159

ABSTRACT

A method is described for determining amphotericin B in plasma using second-derivative spectrophotometry after deproteinization. The assay was based on the absorbance at 407.5 nm. The second-derivative spectrum recorded between 350 and 450 nm allowed identification of the analyte and showed absence of drug interference. Only bilirubin interfered at high concentration (> or = 50 mumol l-1. The linear concentration ranges were 0.05 -5.0 mg l-1 (r = 0.999, slope = 2.731, intercept = 0.008). Between-day CV < or = 9.7%, within-day CV < or = 5.5%, analytical recovery close to 100% were suitable for clinical investigations. This method provides better specificity than direct absorbance, is simpler and faster than a high performance liquid chromatography assay and can be used routinely by any laboratory possessing a spectrophotometer with a derivative accessory.


Subject(s)
Amphotericin B/blood , Spectrophotometry/methods , Drug Stability , Humans , Linear Models , Reproducibility of Results , Sensitivity and Specificity
4.
Ann Biol Clin (Paris) ; 52(7-8): 547-53, 1994.
Article in French | MEDLINE | ID: mdl-7840431

ABSTRACT

Retinol (vit A) and alpha-tocopherol (vit E), the active compounds of vitamins A and E, were assayed by reversed-phase high performance liquid chromatography (HPLC) (C18) with UV absorbance detection at 280 nm. Plasma was deproteinized and liquid-liquid extraction performed with hexane. After evaporation, the residue was dissolved in organic solvents (ether:methanol 25:75, V/V). Standard curves were prepared by adding known amounts of standards to plasma. The use of acetonitrile in the mobile phase (acetonitrile:methanol:water 64.5:33:2.5, V/V) avoided interference peaks, giving a total run time of 8 min. Analyte stability required that samples be treated in the dark. Analytical performance was good: recovery around 100%, detection limits 0.015 mg/l for vit A and 0.030 mg/l for vit E, linear range 2 mg/l for vit A and 20 mg/l for vit E, no recorded interference, and between-run and within-run precision with coefficients of variation < 11%. Analytes were stable at room temperature for 24 h (vit A) and 48 h (vit E) in plasma stored in the dark for one month at -20 degrees C. The standard solution containing both vit A and vit E increased vit A stability. Plasma concentrations (mg/l) for vit A and E were respectively: 0.63 +/- 0.17 and 9.61 +/- 3.1 in adults (n = 29), 0.39 +/- 0.17 et 7.10 +/- 2.41 in children 0 to 15 years (n = 21). This method allows regular monitoring of patients with cystic fibrosis to check for retinol and alpha-tocopherol deficiencies. The usefulness and results of the method are discussed in terms of previous studies.


Subject(s)
Chromatography, High Pressure Liquid/methods , Vitamin A/blood , Vitamin E/blood , Adolescent , Adult , Child , Child, Preschool , Cystic Fibrosis/blood , Humans , Infant , Infant, Newborn
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