• MeSH
• statistika jako téma MeSH

• Konspekt
• Statistika
• NLK Obory
• statistika, zdravotnická statistika

Capillary electrophoresis (CE) was employed for the determination of thermodynamic acidity constants (pKa ) and actual ionic mobilities of polycationic antimicrobial peptides (AMPs). The effective electrophoretic mobilities of AMPs were measured by CE in a series of the background electrolytes within a wide pH range (2.00-12.25), at constant ionic strength (25 mM) and ambient temperature, using polybrene coated fused silica capillaries to suppress sorption of cationic AMPs to the capillary wall. Eventually, Haarhoff-Van der Linde peak fitting function was used for the determination of correct migration times of some AMPs peaks that were distorted by electromigration dispersion. The measured effective mobilities were corrected to 25°C. Mixed acidity constants, pKa,i mix , and actual ionic mobilities, mi , of AMPs were determined by the nonlinear regression analysis of pH dependence of their effective mobilities. The pKa,i mix values were recalculated to thermodynamic pKa s using the Debye-Hückel theory. Thermodynamic pKa of imidazolium group of histidine residues was found to be in the range 3.72-4.98, pKa of α-NH3(+) group was in the range 6.14-6.93, and pKa of ε-NH3(+) group of lysine spanned the interval 7.26-9.84, depending on the particular amino acid sequence of the AMPs. Actual ionic mobilities of AMPs with positive charges from one to six elementary units achieved values (9.8 - 36.5) × 10(-9) m(2) V(-1) s(-1) .

• MeSH
• aminokyseliny chemie   MeSH
• elektroforéza kapilární metody   MeSH
• kationické antimikrobiální peptidy analýza   chemie   MeSH
• koncentrace vodíkových iontů MeSH
• nelineární dynamika MeSH
• osmolární koncentrace MeSH
• termodynamika MeSH
• Publikační typ
• časopisecké články MeSH

• MeSH
• lineární modely MeSH
• statistika jako téma MeSH

• Konspekt
• Statistika
• NLK Obory
• statistika, zdravotnická statistika

CZE has been applied to determination of thermodynamic acidity constants (pKa ) of ionogenic groups and actual ionic mobilities of polyprotic peptides-synthetic human and salmon gonadotropin-releasing hormones and their derivatives and fragments. First, the mixed acidity constants, pKa,imix, of ionogenic groups, and actual ionic mobilities, mi , of gonadotropin-releasing hormone peptides were determined by nonlinear regression analysis of pH dependence of their effective electrophoretic mobilities. The effective mobilities were measured by CZE in a series of BGEs within a broad pH range (1.80-12.10), at constant ionic strength (25 mM) and reference temperature (25°C). Second, the pKa,imix values were recalculated to thermodynamic pKa s using the Debye-Hückel theory. Thermodynamic pKa of carboxyl groups was estimated to be in the range of 2.5-3.3 for C-terminal amino acids of the above peptides, and 5.2 for glutamic acid in the middle of peptide chain; pKa of imidazolyl group of histidine residues was in the range of 5.7-6.8, pKa of N-terminal amino group of the peptide with free N-terminus was equal to 6.2, pKa of phenol group of tyrosine residues was in the range of 9.8-10.8, and pKa of guanidinyl group or arginine residues reached values 11.1-11.3, depending on the position of the residues in the peptide and on the amino acid sequence of the peptide. Absolute values of actual ionic mobilities of peptides with charge number ±2 were in the range (14.6-18.6) × 10(-9) m(2) V(-1) s(-1) , and ionic mobilities of peptides with charge number ±1 reached values (6.5-12.9) × 10(-9) m(2) V(-1) s(-1) .

• MeSH
• elektroforéza kapilární metody   MeSH
• hormon uvolňující gonadotropiny chemie   MeSH
• ionty chemie   MeSH
• koncentrace vodíkových iontů MeSH
• lidé MeSH
• losos MeSH
• nelineární dynamika MeSH
• termodynamika MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

AIMS: While the effect of different types of incontinence on the quality of life (QoL) has been clearly documented, the information about the impact of incontinence severity on QoL in women is lacking. Therefore, we investigated whether increasingly severe degrees of incontinence were linearly correlated with poorer QoL. METHODS: We included 391 incontinent women and 81 continent volunteers in the study and assessed them in accordance with routine clinical practice. A 24 h pad-weight test was used to objectively quantify the incontinence severity. We then stratified participants according to incontinence type and severity and assessed correlations between incontinence severity and Patient Perception of Bladder Condition (PPBC), International Consultation on Incontinence short-form questionnaire (ICIQ-SF), and King's Health Questionnaire (KHQ) quality of life scores in the entire study population and in individual groups according to incontinence type. RESULTS: Minimal incontinence was associated with significant negative impact on QoL, as measured by all quality of life assement tools. There were nonlinear correlations between scores on individual questionnaires and daily leakage volumes. Stress urinary incontinence had a weaker impact on quality of life than urge or mixed incontinence, as measured by PPBC (P < 0.0001), KHQ part 1 (P < 0.0001), and KHQ part 2 (P < 0.001). Stress urinary incontinence also had a weaker impact on QoL than mixed incontinence as measured by ICI-Q (P = 0.007). CONCLUSIONS: This study demonstrated that even mild urinary leakage significantly reduces the QoL, while subsequent increase in the degree of incontinence has only minimal additional effect. There was no linear correlation between incontinence severity and QoL.

• MeSH
• dospělí MeSH
• inkontinence moči psychologie   MeSH
• kvalita života * MeSH
• lidé středního věku MeSH
• lidé MeSH
• nelineární dynamika MeSH
• průzkumy a dotazníky MeSH
• senioři MeSH
• stresová inkontinence moči psychologie   MeSH
• urgentní inkontinence psychologie   MeSH
• vložky pro inkontinentní pacienty MeSH
• zdraví dobrovolníci pro lékařské studie MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Česká republika MeSH

AIMS: Abiraterone treatment requires regular drug intake under fasting conditions due to pronounced food effect, which may impact patient adherence. The aim of this prospective study was to evaluate adherence to abiraterone treatment in patients with prostate cancer. To achieve this aim, an abiraterone population pharmacokinetic model was developed and patients' adherence has been estimated by comparison of measured levels of abiraterone with population model-based simulations. METHODS: A total of 1469 abiraterone plasma levels from 83 healthy volunteers collected in a bioequivalence study were analysed using a nonlinear mixed-effects model. Monte Carlo simulation was used to describe the theoretical distribution of abiraterone pharmacokinetic profiles at a dose of 1000 mg once daily. Adherence of 36 prostate cancer patients treated with abiraterone was then evaluated by comparing the real abiraterone concentration measured in each patient during follow-up visit with the theoretical distribution of profiles based on simulations. Patients whose abiraterone levels were ˂5th or ˃95th percentile of the distribution of simulated profiles were considered to be non-adherent. RESULTS: Based on this evaluation, 13 patients (36%) have been classified as non-adherent. We observed significant association (P = .0361) between richness of the breakfast and rate of non-adherence. Adherent patients reported significantly better overall condition in self-assessments (P = .0384). A trend towards a higher occurrence of adverse effects in non-adherent patients was observed. CONCLUSIONS: We developed an abiraterone population pharmacokinetic model and proposed an advanced approach to medical adherence evaluation. Due to the need for administration under fasting conditions, abiraterone therapy is associated with a relatively high rate of non-adherence.

• MeSH
• adherence k farmakoterapii * statistika a číselné údaje   MeSH
• androsteny * farmakokinetika   aplikace a dávkování   terapeutické užití   MeSH
• biologické modely * MeSH
• dospělí MeSH
• interakce mezi potravou a léky MeSH
• lidé středního věku MeSH
• lidé MeSH
• metoda Monte Carlo MeSH
• nádory prostaty * farmakoterapie   MeSH
• omezení příjmu potravy MeSH
• prospektivní studie MeSH
• protinádorové látky farmakokinetika   aplikace a dávkování   MeSH
• senioři MeSH
• terapeutická ekvivalence MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• Publikační typ
• časopisecké články MeSH

This study aimed to develop a vancomycin population pharmacokinetic model in obese adult patients treated with intermittent haemodialysis and propose a model-based loading dose strategy ensuring attainment of newly recommended AUC-based PK/PD target. Retrospective cross-sectional analysis was performed among obese haemodialysis dependent adult patients treated with intravenous vancomycin. A pharmacokinetic population model was developed using a nonlinear mixed-effects modelling approach and Monte Carlo simulations were used to identify the optimal loading dose for PK/PD target attainment during the first 48 h of treatment. Therapeutic drug monitoring data from 27 patients with a BMI of 30.2-52.9 kg/m2 were analysed. Among all tested variables, only LBM as a covariate of vancomycin Vd significantly improved the model, while vancomycin CL did not correlate with any of the tested variables. The median (IQR) value from the conditional mean of individual estimates of Vd and CL was 68.4 (56.6-84.2) L and 0.86 (0.79-0.90) L/h, respectively. To ensure optimal vancomycin exposure during the first 48 h of therapy, the vancomycin loading dose of 1500, 1750, 2000, 2250, 2500 and 2750 mg should be administered to obese patients with a lean body mass of ˂50, 50-60, 60-70, 70-80, 80-85 and >85 kg, respectively.

• MeSH
• antibakteriální látky * farmakokinetika   aplikace a dávkování   MeSH
• biologické modely MeSH
• dialýza ledvin * MeSH
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• metoda Monte Carlo MeSH
• monitorování léčiv MeSH
• obezita * komplikace   MeSH
• průřezové studie MeSH
• retrospektivní studie MeSH
• senioři MeSH
• vankomycin * farmakokinetika   aplikace a dávkování   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

This study aimed to explore pharmacokinetics of voriconazole and its covariates in lung transplant recipients using population approach in order to propose dosing individualization. Data from routine therapeutic drug monitoring in adult lung transplant recipients treated with oral voriconazole were analysed with a three-stage population pharmacokinetic model using nonlinear mixed-effects modelling. Monte Carlo simulations based on final voriconazole pharmacokinetic model were used to generate the theoretical distribution of pharmacokinetic profiles at various dosing regimens. A total of 78 voriconazole serum concentrations collected from 40 patients were included in pharmacokinetic analysis. The only significant covariate was age for voriconazole clearance. Population voriconazole apparent clearance started at 32.26 L/h and decreased by 0.021 L/h with each year of patient's age, while population apparent volume of distribution was 964.46 L. Based on this model, we have proposed an easy-to-use dosing regimen consisting of a loading dose of 400 mg every 12 h for the first 48 h of treatment followed by maintenance dose of 300 mg every 12 h in patients aged up to 59 years, or by maintenance dose of 200 mg every 12 h in patients aged above 59 years.

• MeSH
• biologické modely MeSH
• dospělí MeSH
• lidé MeSH
• metoda Monte Carlo MeSH
• monitorování léčiv * MeSH
• plíce MeSH
• příjemce transplantátu * MeSH
• senioři MeSH
• vorikonazol farmakokinetika   MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• senioři MeSH
• Publikační typ
• časopisecké články MeSH

• MeSH
• epidemiologická měření MeSH
• infekční nemoci MeSH

• Konspekt
• Patologie. Klinická medicína
• NLK Obory
• infekční lékařství
• epidemiologie

Two novel methods for determination of binding constants in the systems with borate and cyclodextrin complexation were developed. The methods enable to determine all binding parameters in these systems and even the binding constants of interaction of a neutral analyte with a neutral cyclodextrin. The first method is based on nonlinear fitting of experimental data and further evaluation of fitting parameters. The second method requires a multiple regression. The methods provide identical results with low experimental error. Only one set of measurements is required for both methods. Thus the binding parameters can be mutually compared. The binding parameters for neutral analytes ((R,R)-(+)-hydrobenzoin and (S,S)-(-)-hydrobenzoin) and neutral cyclodextrin (heptakis(2,6-di-O-methyl)-β-cyclodextrin) were evaluated and the effect of individual types of interaction was revealed. The interaction of the analytes with cyclodextrin governs the chiral recognition, while the complexation of analyte with borate is responsible for electromigration. Very low values of the binding constants of mixed analyte-cyclodextrin-borate complexes indicate that this type of complexation has negligible effect on enantioseparation.

• MeSH
• benzoin analogy a deriváty   chemie   MeSH
• beta-cyklodextriny chemie   MeSH
• boritany chemie   MeSH
• chemické modely MeSH
• elektroforéza kapilární MeSH
• kinetika MeSH
• regresní analýza MeSH
• stereoizomerie MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH