K Ary

Semmelweis University, Budapest, Budapest fovaros, Hungary

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Publications (13)16.92 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: The pharmacokinetics of nerisopam and its N-acetyl metabolite were examined in parallel by means of a validated solid phase extraction high-performance liquid chromatographic method.Nerisopam was absorbed rapidly and could be measured in plasma for about 8 h. It could be described by a two-compartment open model in rats. The peak plasma concentration of the N-acetyl metabolite was reached rapidly a little later than the parent compound and could be measured for about 12 h. The pharmacokinetics of N-acetyl metabolite could be described by a one-compartment open model.The fast appearance of the metabolite and the higher Cmax and AUC0-∞ values than nerisopam suggest an intensive first-pass metabolism. The increase in the AUC∞-dose ratio with increase in dose suggests that the elimination of the metabolite is concentration-dependent.
    Pharmacy and Pharmacology Communications. 03/2011; 4(4):225 - 228.
  • K Ary, K Róna
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    ABSTRACT: A reversed-phase high-performance liquid chromatographic method with coulometric and UV detection has been developed for the simultaneous determination of morphine, morphine-3-glucuronide and morphine-6-glucuronide. The separation was carried out by using a Supelcosil LC-8 DB reversed-phase column and 0.1 M potassium dihydrogen phosphate (pH 2.5)--acetonitrile--methanol (94:5:1 v/v) containing 4 mM pentanesulfonic acid as the mobile phase. The compounds were determined simultaneously by coulometry for morphine and with UV detection for morphine-3-glucuronide and morphine-6-glucuronide. Morphine, morphine glucuronides and the internal standard were extracted from human plasma using Bond-Elut C18 (1 ml) solid-phase extraction cartridges. In the case of coulometric detection, the detection limit was 0.5 ng/ml for morphine; in the case of UV detection the detection limit was 10 ng/ml for morphine-3-glucuronide and for morphine-6-glucuronide, too.
    Journal of Pharmaceutical and Biomedical Analysis 10/2001; 26(2):179-87. · 2.83 Impact Factor
  • K Róna, K Ary
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    ABSTRACT: A rapid, simple reversed-phase high-performance liquid chromatographic method with ultraviolet absorbance detection has been developed for the determination of calcium dobesilate in human plasma. Sample processing is based on an ion-pairing extraction with tetra-n-butylammonium hydroxide as cationic pairing ion and dichloromethane. Separation of the investigated calcium dobesilate and 2,4-dihydroxybenzoic acid as internal standard was achieved on a Discovery RP-Amide C16 analytical column with 50 mM, pH 2.5, potassium dihydrogenphosphate buffer-acetonitrile (75:25, v/v) mobile phase. The wavelength was set at 305 nm. The limit of quantitation is 100 ng/ml and the calibration curve is linear up to 50 microg/ml. Within-day and between-day precision expressed as the relative standard deviation is about 10% and the accuracy of the determination did not deviate from 100% by more than +/-10%. The developed method was found to be suitable for application in human bioequivalence studies.
    Journal of chromatography. B, Biomedical sciences and applications 06/2001; 755(1-2):245-51.
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    ABSTRACT: In a single dose, randomized, cross-over study, with one week of wash-out period, the relative bioavailability of Dopegyt tablets containing 250 mg alpha-methyldopa (AMD) and Presinol film tablets with identical active ingredient content was examined in 24 healthy volunteers. Since technologically two completely different preparations (a film-tablet and a non-film-tablet) having significantly different in vitro dissolution were to be compared, both preparations were compared to a third one, AMD solution (Dopegyt solution) with 250 mg/50 ml concentration. Plasma concentrations of the drug were measured for 24 hours post-dose, applying HPLC with fluorometric detection. Pharmacokinetic parameters calculated from individual data (AUC0-infinity, AUC0-t, Cmax, Cmax/AUC0-infinity, t(max)) were evaluated statistically. Wilcoxon's nonparametric test and the four-way variance analysis could not detect any significant difference at the usual a=95% probability level in these pharmacokinetic parameters of the two tablet preparations. For AUC0-infinity at the 90% probability level, the confidence interval was 0.883-1.237 (with an estimated geometric mean of 1.045), for the test/reference ratio of Dopegyt and Presinol tablets, thus the two preparations proved to be bioequivalent. The relative bioavailability of Dopegyt (test preparation) and Presinol (reference preparation) calculated from the AUC0-infinity values was 116.7+/-56.7% that also confirmed bioequivalence. The results of all the applied statistical tests suggest that Dopegyt and Presinol can be considered as bioequivalent preparations.
    European Journal of Drug Metabolism and Pharmacokinetics 03/2001; 26(1-2):25-30. · 1.31 Impact Factor
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    ABSTRACT: A reversed-phase high-performance liquid chromatographic method with electrochemical detection has been developed for the determination of buspirone from human plasma. The separation was carried out by using a Supelcosil ABZ+ plus C18 reversed-phase column and 0.05 M potassium dihydrogenphosphate (pH 6.5)-acetonitrile (7:3, v/v) as the mobile phase. The compounds were detected by coulometry. Buspirone and the internal standard were extracted from the human plasma using Bond-Elut C18 solid-phase extraction cartridges. Following removal of the the highly lipophilic plasma components we applied a column-switching technique which reduced the duration of HPLC measurement from 60 min to 15 min. The limit of quantitation was found to be 100 pg/ml plasma.
    Journal of Chromatography A 02/1998; 797(1-2):221-6. · 4.26 Impact Factor
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    ABSTRACT: A simple high-performance liquid chromatographic method with ultraviolet absorbance detection has been developed to determine the concentration of N-3-(2,2,5,5-tetramethyl-3-pirrolin-3-carboxamidopropylphthalim ide hydrochloride; A-2545), a new antiarrhythmic agent from human plasma. Separation of the investigated compound and internal standard was achieved on a Nucleosil 7 C18 column with a 0.01-M potassium dihydrogenphosphate buffer (pH 2.5)-methanol (60:40, v/v) mobile phase. The detection was performed at 220 nm. During the determinations, buspirone served as the internal standard. The compounds were isolated from plasma on a Bakerbond C18 solid-phase extraction cartridge and the mean absolute recovery was 92.9%. The limit of quantitation was found to be 10 ng/ml. The bioanalytical method was validated with respect to linearity, within- and between-day accuracy and precision, system suitability and stability. All validated parameters were found to be within the internationally required limits. The developed analytical method for A-2545 was found to be suitable for application in pharmacokinetic studies and for human drug monitoring.
    Journal of Chromatography A 02/1998; 797(1-2):265-70. · 4.26 Impact Factor
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    ABSTRACT: A simple high-performance liquid chromatographic method for determination of ticlopidine in human plasma using UV detection was developed. The separation of the investigated compound and internal standard was achieved on "BST Rutin" 10, C18 BD column with a 0.01 M, (pH 4) potassium dihydrogen phosphate bufferacetonitrile-methanol (20:40:40 v/v) mobile phase. The detection was performed at 215 nm. The compounds were isolated from plasma by Bond Elut C18 solid-phase extraction, the mean absolute recovery was 84.9%. The limit of quantitation was 10 ng/ml, the limit of detection was 5 ng/ml. The assay has been validated with respect to accuracy, precision and system suitability. All validated parameters were found to be within the necessary limits. The developed analytical method for ticlopidine was found to be suitable for application in pharmacokinetic studies and human drug monitoring.
    Acta pharmaceutica Hungarica 02/1997; 67(1):25-9.
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    ABSTRACT: It was established during the human phase I study of nerisopam, a new anxiolytic drug, that nerisopam (EGIS-6775) shows two, while N-acetyl metabolite (EGIS-7649) shows one compartmental pharmacokinetic behaviour. Acetylation of nerisopam is polymorph, so that volunteers belonging into slow or fast acetylating group show significantly different plasma concentration. Observed pharmacokinetic differences are primarily manifested in the absorption phase, and not in the elimination one. Accordingly, slow acetylators have higher nerisopam levels, while fast acetylators possess higher metabolite levels. Elimination phase is practically parallel for both compounds. At the same time, significant differences are found in the AUC and Cmax values. Nerisopam is rapidly absorbed, but N-acetyl metabolite is appeared especially fast in the blood. Our consideration is, that nerisopam undergoes significant "first-pass" metabolism process, the extent of which is different between the two acetylator phenotypes.
    Acta pharmaceutica Hungarica 01/1997; 67(2-3):65-71.
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    ABSTRACT: Three doses were administered to the rats during the pharmacokinetic study of nerisopam and the plasma concentrations of nerisopam and its N-acetyl metabolite were determined parallelly by means of validated SPE-HPLC method developed by the authors. The pharmacokinetics of nerisopam could be described by a two-compartment open model in rats, it was absorbed rapidly and could be measured in plasma for about 8 hours. The peak plasma concentration of the N-acetyl metabolite was reached rapidly a little bit later than that of the parent compound, similarly to the human plasma, and it could be measured for about 12 hours. The pharmacokinetics of N-acetyl metabolite could be described by an one-compartment open model. The fast appearance of the metabolite and the Cmax and AUC 0-infinity values higher than those of nerisopam refer to an intensive "first-pass" metabolism. The AUC-dose curves indicate that supposingly the mechanism transforming the N-acetyl metabolites are not as fast as the acetylation.
    Acta pharmaceutica Hungarica 01/1997; 67(2-3):59-63.
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    ABSTRACT: A sensitive reversed-phase gradient elution high-performance liquid chromatographic method with fluorescence detection has been developed for the determination of alpha-methyldopa (AMD) in human plasma. Separation of the investigated compound and the 3,4-dihydroxyphenylalanine (DOPA) internal standard was achieved on a Nucleosil 7 C18 column with a 5 mM heptanesulphonic acid sodium salt containing 0.05 M potassium dihydrogenphosphate (pH 3.2)-acetonitrile mobile phase. The composition of the mobile phase was changed according to a linear gradient time program. Detection was performed at 270 nm fluorimetric excitation and 320 nm emission. The compounds were isolated from plasma by Bond-Elut C18 solid-phase extraction. The limit of quantitation was found to be 10 ng/ml plasma. The assay was validated with respect to accuracy, precision and system suitability. All validated parameters were found to be within the 20% required limits. On the basis of the sensitivity, linearity and validation parameters the developed analytical method was found to be suitable for application in a bioequivalency study.
    Journal of Chromatography A 05/1996; 730(1-2):125-31. · 4.26 Impact Factor
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    ABSTRACT: A sensitive reversed-phase high-performance liquid chromatographic method with ultraviolet absorbance detection has been developed to simultaneously determine the concentrations of nerisopam (EGIS-6775) and its N-acetyl metabolite (EGIS-7649) from human plasma. The separation of the investigated compounds and internal standard was achieved on a Nucleosil 7 C(18) column with 2 mM heptanesulphonic acid containing 0.04 M phosphoric acid-acetonitrile-methanol (70:25:5, v/v), pH 2.7 mobile phase. The detection was performed at 385 nm. The compounds were isolated from plasma by Bakerbond C(18) solid-phase extraction. The limit of quantitation was 10 ng/ml plasma for each compound investigated. The assay has been validated with respect to accuracy, precision and system suitability. All validated parameters were found to be within the necessary limits. On the basis of the sensitivity, linearity and validation parameters, the developed analytical method was found to be suitable for the determination of nerisopam and its N-acetyl metabolite from human plasma and for application in pharmacokinetic studies and human drug monitoring. The pharmacokinetic parameters obtained from twelve human volunteers are reported. It was found that nerisopam acetylation is polymorphic: the volunteers with fast or slow acetylator phenotypes produced significantly different plasma concentrations. In slow acetylator phenotypes the concentration of nerisopam was considerably higher in plasma, while the level of its acetyl metabolite was higher in plasma of fast acetylators.
    Journal of chromatography. B, Biomedical applications 04/1996; 678(1):63-72.
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    ABSTRACT: The authors studied the distribution of the paracetamol conjugation in a Hungarian population (53 adult Caucasian persons). The data indicated that the excretion of paracetamol glucuronide and sulphate were not normally distributed. Bimodality were apparent in both conjugation pathways: 15.1% of subjects was relatively extensive glucuronidators, and the 24.5% of subjects was extensive sulphatators. Monitoring the ratios of various urinary paracetamol conjugates/paracetamol may be useful as a tool for determining the glucuronide and sulphate conjugation capacity in humans.
    Acta medica Hungarica 02/1994; 50(1-2):65-74.
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    ABSTRACT: The authors discuss the validation of bioanalytical methods used to generate data for bioavailability, bioequivalence and pharmacokinetics studies. The basis of this manuscript is a consensus on the requirements for bioanalytical validation, which has been reached by a panel of experts at the Washington Conference Report. In this paper it is attempted to suggest approaches to validation parameters both for the method and assay to be evaluated, namely specificity/selectivity, linearity, LOQ/LOD, accuracy, prescision, recovery and stability.
    Acta pharmaceutica Hungarica 67(2-3):51-7.