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Biomedical subjects

F Perlík

Publications and source records attributed to F Perlík.

At least 19 recordsLinked to original sources
PubMed2006

Miotic action of tramadol is determined by CYP2D6 genotype.

Polymorphic CYP2D6 is the enzyme that activates the opioid analgesic tramadol by O-demethylation to its active metabolite O-demethyltramadol (M1). Our objective was to determine the opioid effects measured by pupillary response to tramadol of CYP2D6 genotyped volunteers in relation to the disposition of tramadol and M1 in plasma. Tramadol displayed phenotypic pharmacokinetics and it was possible to identify poor metabolizers (PM) with >99% confidence from the metabolic ratio (MR) in a single blood sample taken between 2.5 and 24 h post-dose. Homozygous extensive metabolizers (EM) differed from PM subjects by an almost threefold greater (P=0.0014) maximal pupillary constriction (Emax). Significant correlations between the AUC and Cmax values of M1 versus pupillary constriction were found. The corresponding correlations of pharmacokinetic parameters for tramadol itself were weaker and negative. The strongest correlations were for the single-point metabolic ratios at all sampling intervals versus the effects, with rs ranging from 0.85 to 0.89 (p<0.01). It is concluded that the concept of dual opioid/non-opioid action of the drug, though considerably stronger in EMs, is valid for both EM and PM subjects. This is the theoretical basis for the frequent use and satisfactory efficacy of tramadol in clinical practice when given to genetically non-selected population.

Adult↗
PubMed2006

Polymorphisms of the MDR1 gene in the Czech population.

There exists a marked inter-individual variability of P-glycoprotein expression and activity, which can be of clinical importance due to the large number of drugs that are substrates for the transporter. Previously identified polymorphisms in the MDR1 gene belong to important factors causing this phenomenon. Our aim was to investigate the frequency of major functional SNPs of the MDR1 gene coding for P-glycoprotein in the Czech population. DNA was isolated from whole blood of 189 healthy, young and unrelated subjects (99 females and 90 males, aged from 23 to 28 years). The genotypes of polymorphic positions C3435T, G2677T/A, C1236T and T-76A were determined by PCR-RFLP. Observed allelic frequencies were 56.5%, 46.0%, 0.53%, 44.5% and 37.6% for the alleles 3435T, 2677T, 2677A, 1236T and -76A, respectively. We have found 64 subjects homozygous for 3435T, 42 for 2677T, 40 for 1236T and 31 for -76A alleles. The allelic distribution complies well with Hardy-Weinberg equilibrium. Allelic frequencies of functionally important MDR1 variants are in the Czech population similar to that of other Caucasian populations.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2005

[Infrared pupilometry measured by digital photography].

BACKGROUND: Pupil size is mainly controlled by the action of parasympathetic and sympathetic nerves. Measurement of pupil size and reaction to light are important in both experimental and clinical settings. METHODS AND RESULTS: We have established infrared pupilometry using a commercially available digital camera and a calculation with standard computer software. Volunteers were habituated in a dark room for five minutes before pupil evaluation. Pupil measurement was repeated three times and the diameter was calculated according to the following formula: D(mm)=30/S(pix)*D(pix), where D(pix) and D(mm) represent the pupil size in pixels and millimetres, respectively, and S(pix) was the length in pixels of a 30 mm standard. Our method was validated by the measurement of the diameter of calibration circles printed on a white sheet of paper. Deviation from the actual size was less than 3%. We also compared the results of pupil size obtained by our method, with the results of the pupilometer Pupillscan II measurement. The relative difference between the two methods was always less than 5%. The applicability of the method was illustrated by measurement of the pharmacodynamic effect of the single dose of tramadol (100 mg p.o.) in seven volunteers, compared with control placebo-treated volunteers. CONCLUSIONS: The proposed method is precise and sensitive enough to be used for pupil size determination.

Adult↗
PubMed2004

[Adverse effects and drug interactions].

Adverse drug reactions represent a common clinical problem. They are partly induced by a large variability in drug response, which results from the complex interplay between pharmacokinetics, pharmacodynamics and other disease-associated factors. The review describes metabolic changes caused by polymorphism in the cytochrome P450 and gives examples of induction and inhibition of this enzyme system in relation to adverse drug interaction. From the clinical point of view, attention should be paid especially to antidiabetics, anticoagulants and phenytoin. Therapeutic drug monitoring and genetic-based individualization of the therapy with polymorphically metabolized drugs with narrow therapeutic range can contribute to the decreased incidence of adverse drug reactions.

Cytochrome P-450 Enzyme System↗
PubMed2002

[Evaluation of trends in ue of antibiotics and resistance in selected bacterial pathogens].

BACKGROUND: Evaluation of antibiotic consumption and the surveillance of bacterial pathogens resistance appears to be an indispensable part of antibiotic policy. The aim of this study was to evaluate dynamics of antibiotics consumption and resistance development in selected bacterial strains (Pseudomonas aueruginosa, Staphylococcus aureus and Staphylococcus epidermidis) in the environment of Faculty Hospital. METHODS AND RESULTS: The analysis was focused on the development of antibiotic consumption and monitoring of the development of bacterial resistance. Samples were taken in internal and surgical departments of General Faculty Hospital in Prague in 1992, 1995, and 1999. The evaluation of antibiotic consumption was based on Anatomical Therapeutic and Chemical classification system and the Defined Daily Doses (DDD). The consumption in the follow up period almost doubled in surgical department while in internal medicine department was decreased by almost one third. In both department, namely in the surgical one significant increase of bacterial resistance of tested antibiotics was noted. CONCLUSION: The important part of the local antibiotic policy is the monitoring of development of bacterial resistance and consumption of antibiotics.

Anti-Bacterial Agents↗
PubMed2002

High-performance liquid chromatographic determination of tramadol and its O-desmethylated metabolite in blood plasma. Application to a bioequivalence study in humans.

Simultaneous HPLC determination of the analgetic agent tramadol, its major pharmacodynamically active metabolite (O-desmethyltramadol) in human plasma is described. Simple methods for the preparation of the standard of the above-mentioned tramadol metabolite and N1,N1-dimethylsulfanilamide (used as the internal standard) are also presented. The analytical procedure involved a simple liquid-liquid extraction of the analytes from the plasma under the conditions described previously. HPLC analysis was performed on a 250x4 mm chromatographic column with LiChrospher 60 RP-selectB 5-microm (Merck) and consists of an analytical period where the mobile phase acetonitrile-0.01 M phosphate buffer, pH 2.8 (3:7, v/v) was used, and of a subsequent wash-out period where the plasmatic ballast compounds were eluted from the column using acetonitrile-ultra-high-quality water (8:2, v/v). The whole analysis, including the equilibration preceding the initial analytical conditions lasted 19 min. Fluorescence detection (lambda(ex) 202 nm/lambda(em) 296 nm for tramadol and its metabolite, lambda(ex) 264 nm/lambda(em) 344 nm for N1,N1-dimethylsulfanilamide) was used. The validated analytical method was applied to pharmacokinetic studies of tramadol in human volunteers.

Analgesics, Opioid↗
PubMed2002

Attitude of Czech physicians to adverse drug reaction reporting.

This survey was carried out to test physicians' knowledge of the principles of adverse drug reaction (ADR) reporting. Structured interviews were carried out with 500 physicians in all regions of the Czech Republic. The questions were aimed at observing ADR, the obligation and the means of reporting, and the source of drug information used in practice. Ninety percent (n=448) reported that they faced ADR in their practice, and 92% (n=458) were aware of the obligation to report, but most (180 general practitioners, 138 specialists) were unclear as to what should be reported. Knowledge of the subject of ADR reporting was significantly lower (18.4%) among physicians who used primarily the drug information provided by pharmaceutical companies than among those who used other information sources (38.4%). The low level of knowledge of ADR spontaneous reporting system found in our study is one of the reasons for the substantial underreporting of ADR in the Czech Republic compared to other European countries.

Adverse Drug Reaction Reporting Systems↗
PubMed2002

Noninvasive evaluation of portal-systemic shunting by glyceryl trinitrate.

Portal-systemic shunting is an important circulatory abnormality in patients with liver cirrhosis. Glyceryl trinitrate (GTN) that is normally subject to first pass elimination, may exhibit higher bioavailability in these patients. This study compares the pharmacodynamic effects of GTN after peroral and sublingual administration for noninvasive assessment of shunting. Six control subjects and 15 patients with cirrhosis were studied after oral and sublingual application of 0.5 mg of GTN. Liver cirrhosis was complicated by portal hypertension in 7 of the patients and 4 patients had surgically implanted portocaval anastomosis. Digital plethysmography, which is highly sensitive and is essentially noninvasive in nature, was used to assess and compare the pharmacodynamic effects of GTN. The following values of the ratio of areas under the pharmacodynamic effects/time curve were obtained: 0.08 +/- 0.06 in healthy subjects, 0.52 +/- 0.21 in patients with uncomplicated cirrhosis, 0.99 +/- 0.34 in patients with portal hypertension and 1.24 +/- 0.43 in patients with portal-systemic shunts. We conclude that increased bioavailability of GTN reflects portal-systemic shunting and might be used providing that the pharmacodynamic data reflect both pharmacokinetic variability and the pharmacokinetic-pharmacodynamic interrelations.

Administration, Oral↗
PubMed2001

[Use of the paraxanthine/caffeine ratio in the saliva of patients with liver cirrhosis].

BACKGROUND: Caffeine elimination and monitoring of its metabolites after a single peroral administration in used to evaluate liver metabolic function. The aim of the study was to use the paraxanthine/caffeine ratio in saliva to evaluate liver function in patients with liver cirrhosis. Results were correlated with various procedures evaluating the elimination rate of caffeine. METHODS AND RESULTS: The study group consisted of 7 patients with compensated liver cirrhosis and 10 healthy volunteers, all individuals were given a single 280 mg dose of caffeine perorally. Concentration of salivary caffeine was determined in each person with high performance liquid chromatography after 4, 6, 8 and 12 hours after application. The paraxanthine/caffeine ratio was evaluated at the 6-hour interval. Estimated clearance (CL), half-life (t1/2) and volume of distribution (Vd) were calculated from 2 or 4 concentrations of the drug. The metabolic ratio of the patients (x = 0.15 +/- 0.07) was significantly lower then the control group (x = 0.55 +/- 0.29). Using a four-point procedure we acquired the following values: patients--CL 2.39 +/- 2.36 l/h, t1/2 = 90.18 +/- 168.44 h; healthy volunteers--CL = 8.10 +/- 4.58 l/h, t1/2 = 8.60 +/- 4.12 h (p < 0.05). Statistically significant correlation was found between the metabolic ratio and CL value (rs = 0.83) or between half-life (rs = -0.72). Similar results were also obtained using the two-point method. CONCLUSION: In patients with liver cirrhosis we found significantly lower paraxanthine/caffeine ratio which correlates with lowered elimination of caffeine. Its evaluation enables non-invasive assessment of liver metabolic function from a single sample of saliva.

Caffeine↗
PubMed2001

Phenotype of cytochrome P450 CYP2D6 in patients with familial adenomatous polyposis.

This paper describes an attempt to establish the distribution of the oxidative phenotype of sparteine in patients with familial adenomatous polyposis (FAP). The oxidative polymorphism of sparteine was determined in 30 patients with FAP. One hundred and twenty-six normal subjects were examined as a control group. Subjects with urinary metabolic ratios (MR) greater than 20 (the metabolic ratio of sparteine/dehydrosparteines excreted in urine) were defined as poor metabolizers of sparteine. None of the patients were classified as poor metabolizers of sparteine, although 5 control subjects were. No significant differences were found in the distribution of frequencies between patients and control subjects. However, there was a higher metabolic ratio (mean 1.58 +/- 1.13) in 5 patients with malignant changes in large bowel adenomas compared with other FAP patients without malignant changes (mean MR 0.89 +/- 0.66).

Adenomatous Polyposis Coli↗
PubMed1999

[Evaluation of drug utilization from positive lists].

BACKGROUND: The introduction of positive drug lists (positive lists) is part of the regulating mechanisms which try to reduce the increasing expenditure on drugs. An essential part of these provisions is at present an analysis of the trend of drug consumption. The objective of the work was to introduce and evaluate the method DU 90% which in analyses of drug consumption uses a 90% ratio of preparations of their total consumption. METHODS AND RESULTS: The analysis was focused on prescriptions in medical clinics of the General Faculty Hospital Classification of drugs according to anatomical, therapeutic and chemical groups and the use of defined daily doses made it possible to calculate DU 90% and to prepare a consecutive list of drugs according to costs in different departments. The number of drugs with a defined daily dose was within the range of 280-316. In the interval DU 90% were 116-142 drugs. In all departments there was a practically identical ratio of drugs which were part of the positive list. The greatest expenditure were anti-infectious drugs for systemic use and drugs with an effect an blood and haematopoietic organs. CONCLUSIONS: The advantages of the method DU 90% is its easy application, low cost and possibility to identify controversial lields. This facilitates further qualitative and quantitative evaluation of the standard of pharmacotherapy.

Czech Republic↗
PubMed1997

[Ursodeoxycholic acid in the treatment of primary biliary cirrhosis].

BACKGROUND: Pharmacotherapy of primary biliary cirrhosis (PBC) was not resolved unequivocally so far. During the last decade bile acids are used more widely. The objective of the submitted paper was to investigate under conditions of an open perspective study the influence of long-term administration of ursodeoxycholic acid on the clinical course and selected laboratory indicators. METHODS AND RESULTS: Ursodeoxycholic acid (Ursosan cps PRO.MED.CS) was administered to patients with PBC for a period of three years, 10-12 mg/kg/day. The investigation was completed by 13 women with a confirmed diagnosis of PBC which met clinical, laboratory and morphological criteria. During treatment marked improvement of itching was recorded, a significant drop of serum bilirubin, ALP and ALT. Changes of serum albumin levels were recorded only after three years treatment. The prothrombin time and galactose elimination capacity did not change significantly. Immunoglobulins M remained elevated and antimitochondrial antibodies were detected throughout treatment. The prognosis of the disease was evaluated by means of the Mayo score, the values of which declined significantly during the investigation. No serious side-effects were observed during treatment. CONCLUSIONS: Clinical evaluation proved beyond doubt a favourable effect of ursodeoxycholic acid on clinical and laboratory findings in PBC. Treatment should be started as soon as possible. Long-term continual administration is preferable.

Adult↗
PubMed1996

High-performance liquid chromatographic determination of tramadol in human plasma.

Tramadol has been determined in human plasma samples using a sensitive high-performance liquid chromatographic method. The plasma samples were extracted with tert.-butylmethyl ether in one-step liquid-liquid extraction (recovery 86%) and analyses of the extracts were performed on reversed-phase silica gel using ion-pair chromatography (verapamil as an internal standard) and fluorescence detection. The method was applied to the determination of tramadol levels in twelve healthy volunteers after oral administration of 100 mg of tramadol in capsules of Protradon and Tramal.

Administration, Oral↗
PubMed1995

Phenytoin as a risk factor in gingival hyperplasia.

Fifty-four out-patients with epilepsy who had been taking phenytoin for more than one year were examined for gingival hyperplasia. Approximately 76% of patients showed either mild or no gingival hyperplasia. Lesion severity was then compared statistically to phenytoin dosage and drug concentrations as well as to other clinical and laboratory parameters. There was a tendency for gingival hypertrophy to be associated with both increasing dosage of phenytoin per unit of body weight and the duration of phenytoin administration. All patients followed had a statistically significant progressive trend to increasing gingival hyperplasia with higher total and free phenytoin concentration.

Adult↗
PubMed1994

Pharmacokinetics of ethyl biscoumacetate and its metabolite 7-hydroxy ethyl biscoumacetate in healthy volunteers.

Disposition kinetics of ethyl biscoumacetate and its metabolite 7-hydroxy ethyl biscoumacetate were evaluated in ten healthy volunteers, after a single 300 mg oral dose of ethyl biscoumacetate. Serum concentrations of parent compound and its metabolite were measured by HPLC. The maximum serum ethyl biscoumacetate concentrations were reached 1.0-4.0 hours after drug dosing. From 3 hours after drug administration the concentration of the metabolite was always higher than the concentration of the parent compound. Geometric mean of elimination half-life was 0.66 hours for ethyl biscoumacetate and 2.03 hours for the 7-hydroxy ethyl metabolite.

Administration, Oral↗
PubMed1994

[Determination of caffeine using high-performance liquid chromatography].

The present paper reports a method of caffeine assay in human saliva using high-performance liquid chromatography (HPLC). Samples of saliva were extracted into a mixture of chloroformisopropanol, the extract was evaporated at 40 degrees C and reconstituted with 100 microliters of methanol. The internal standard was 8-chlorotheophylline, the mobile phase consisted of 30 parts of methanol and 70 parts of 0.01 KH2PO4 buffer, the acidity of which was adjusted to pH = 4 conc.H3PO4. The column NUCLEOSIL C18 5 microns, 250 x 4 mm, was employ for separation, UV detection, 254 nm. The chromatograms are shown in Fig. 1. The introduced method was verified when determining caffeine concentrations in patients with liver cirrhosis and in control persons. The results are shown in Table 2. The calibration curve is linear in the range of the concentrations determined from 0.5 to 10 mg/l with the regression coefficient r1,2 = 0.990. Good reproducibility of the method is characterized by the low values of the relative standard deviations (Table 1). The reported manner of caffeine determination in saliva can be utilized to evaluate liver metabolic capacities.

Caffeine↗
PubMed1992

Determination of ethyl biscoumacetate and its metabolite 7-hydroxyethyl biscoumacetate in human serum by high-performance liquid chromatography and mass spectrometry.

An efficient reversed-phase high-performance liquid chromatographic method has been developed for the determination of ethyl biscoumacetate (EBA) and its metabolite in human serum, using the mu Bondapak C18 column and methanol-water-phosphoric acid (56:46.8:0.2, v/v/v) as the mobile phase. This method permitted the determination of both EBA and a metabolite in human serum. The latter has been mentioned by other authors only in urine samples, where significant concentrations were found. Identification of the metabolite as 7-hydroxyethyl biscoumacetate was based on its chromatographic separation, followed by isolation from the eluate and direct mass spectrometric identification. It has been found that the higher EBA concentrations in human serum described by Brodie et al. [J. Pharmacol. Exp. Ther., 106 (1952) 453] were caused by the insufficient resolving power of the spectrophotometric method used, leading to overlapping of the UV spectra of the parent drug and its metabolite.

Chromatography, High Pressure Liquid↗