Objective of the work: The purpose of this quantitative retrospective comparative study was to register possible cases of augmentedted renal clearance (ARC) in patients of Hospital of Lithuanian University of Health Sciences and analyse the differences in assessments of cases of Augmented Renal Clearance and the drug therapy problems related to ARC. Tasks: To achieve the objective, several tasks were performed: 1) to register possible ARC patients cases as assessed by Cocroft-Gault and their possible associated reasons; 2) to analyse differences in three equations used for GFR estimation: Cocroft-Gault, MDRD simplified, and CKD-EPI. 3) compare the therapies of the patients and determine the drugs that are in risk of being underdosed when ARC is present. Methodology: An ARC survey (appendix 1) was filled about patients from various departments of Clinics during the period of 2013 03 04 – 2014 08 15. All patients were selected according serum creatinine values that were 50 µmol/l. or less. Two goups of patients were assigned for analysis: patients were grouped according Cocroft - Gault creatinine clearance values: (1) ARC group A CrCl >130 ml./min and (2) comparative Non-ARC group B CrCl 90-130 ml./min. Data were analyzed by using descriptive and comparative statistical analysis, considering statistically significant difference between the groups if p value was <0.05. Results and conclusions: 1. In the research group and comparative groups were 31 patients selected... [to full text] / Darbo tikslas: Šio kiekybinio retrospektyvaus palyginamojo darbo tikslas buvo surinkti duomenis apie padidinto inkstų klirenso PIK atvejus Lietuvos sveikatos mokslų universiteto ligonines Kauno klinikose. Buvo siekiama išanalizuoti sirtumus tarp skirtingų PIK įvertinimo būdų ir įvertinti galimas su PIK susijusias terapijos problemas. Uždaviniai: norint pasiekti užsibrėžtus tikslus šie uždaviniai buvo iškelti: 1) užregistruoti PIK atvejus ir nustatyti jų galimas priežastis. 2) apskaičiuoti GFG trimis skirtingomis formulėmis (Cocroft-Gault, MDRD, CKD-EPI) ir išanalizuoti skirtumus. 3) palyginti pacientų terapijas ir nustatyti, kurie vaistai galimai yra subterapinio dozavimo rizikoje Metodika: PIK anketa ( 1 priedas) buvo pildoma apie pacientus iš skirtingų Kauno klinikų skyrių, laikotarpiu nuo 2013 03 04 iki 2014 08 15. Visi pacientai buvo parinkti pagal kreatinino kiekį serume – 50 μmol/l.. ir mažiau. Dvi pacientų grupės buvo parinktos analizei: pacientai buvo sugrupuoti pagal kreatinino klirensą į (1) PIK A grupę – CrCl > 130 ml./min. ir (2) palyginamąją B grupę – CrCl 90-130 ml./min. Duomenys buvo analizuojami naudojant palyginamąją ir aprašomąją statistiką. Skirtumai tarp grupių buvo laikomi statistiškai reikšmingi, kai p reikšmė buvo <0.05. Rezultatai ir išvados: 1. Abiejose grupėse buvo surinkta po 31 pacientą (iš viso 62 pacientai). Remiantis darbo rezultatais, galima daryti išvadą, kad PIK (kai GFG yra 130ml/min. ir daugiau) nustatymui naudojant Cocroft-Gault formulę... [toliau žr. visą tekstą]

In recent years, the focus on augmented renal clearance increased as it was found by other researchers to result in subtherapeutic drug dosing concentrations. Accurate assessment of renal function is important for prescribing optimal dosis of pharmaceuticals for ARC patients. Objective of the work: The purpose of this quantitative retrospective comparative study was to register possible cases of Accelerated renal clearance in patients of Hospital of Lithuanian University of Health Sciences Kaunas Clinics and analyse the differences in assessments of cases of Augmented Renal Clearance and the possible risks of ARC for therapy. Tasks: To achieve the objective several tasks were raised: 1) to register possible ARC patients cases as assessed by Cocroft-Gault and their possible associated reasons; 2) to analyse differences in three for GFR estimation used equations (Cocroft-Gault, MDRD simplified, and CKD-EPI). 3) determine the risk drugs for changed renal elimination. Methodology: ARC survey (appendix 1) was filled about patients from various departments of Clinics during the period of 2013 03-04 – 2013 12-20. All patients were selected according serum creatinine values that were 50 µmol/l. or less. Two goups of patients were assigned for analysis: patients were grouped according Cocroft - Gault creatinine clearance values: (1) ARC group A CrCl >130 ml./min and (2) comparative Non-ARC group B CrCl 90-130 ml./min. In the group A were 31 and in the group B - 5 patients... [to full text] / Pastaraisiais metais labai išaugo tyrimų apie padidintą inkstų klirensą (PIK), nes pagal keleto tyrejų duomenis šios būklės pasekmė yra subterapinės vaistų koncentracijos. Tikslus inkstų funkcijos nustatymas yra labai svarbus norint parinkti optimalias terapines vaistų dozes padidinto inkstų klirenso pacientams. Darbo tikslas: Šio kiekybinio retrospektyvaus palyginamojo darbo tikslas buvo surinkti duomenis apie padidinto inkstų klirenso PIK atvejus Lietuvos sveikatos mokslų universiteto ligonines Kauno klinikose. Buvo siekiama išanalizuoti sirtumus tarp skirtingų PIK įvertinimo būdų ir įvertinti galimas PIK rizikas terapijai Uždaviniai: norint pasiekti užsibrėžtus tikslus šie uždaviniai buvo iškelti: 1) užregistruoti PIK atvejus ir nustatyti jų galimas priežastis. 2) apskaičiuoti GFG trimis skirtingomis formulėmis (Cocroft-Gault, MDRD, CKD-EPI) ir išanalizuoti skirtumus. 3) nustatyti vaistus, kurie gali būti pakitusios inksų eliminacijos rizikoje. Metodika: PIK anketa ( 1 priedas) buvo pildoma apie pacientus iš skirtingų Kauno klinikų skyrių, laikotarpiu nuo 2013 04 03 iki 2013 12 20. Visi pacientai buvo parinkti pagal kreatinino kiekį serume – 50 µmol/l.. ir mažiau. Dvi pacientų grupės buvo parinktos analizei: pacientai buvo sugrupuoti pagal kreatinino klirensą į (1) PIK A grupę – CrCl > 130 ml./min. ir (2) palyginamąją B grupę – CrCl 90-130 ml./min. A grupėje buvo parinktas 31 pacientas ir B grupėje 5 pacientai. Rezultatai: Vidutinės GFG reikšmės tiriamojoje... [toliau žr. visą tekstą]

O EPP-AF® é um extrato padronizado de própolis quimicamente caracterizado e com eficácia e segurança pré-clínica estabelecidas. O objetivo principal deste trabalho foi realizar um ensaio clínico de segurança para avaliar a influência do EPP-AF® na atividade da P-gp e das principais isoformas CYP, através de um teste in vivo tipo coquetel de fármacos marcadores administrados em doses subterapêuticas. Foram investigados 16 voluntários adultos sadios antes e após a exposição a 375 mg de EPP-AF® por via oral durante 15 dias. As amostras seriadas de sangue foram colhidas até 12 h após a administração do coquetel contendo midazolam (0,2 mg), cafeína (10 mg), omeprazol (2 mg), metoprolol (10 mg), losartana (2 mg) e fexofenadina (10 mg). Foram desenvolvidos e validados três métodos analíticos empregando LC-MS/MS para quantificar as concentrações plasmáticas de fexofenadina, losartana, E-3174 (método 1), omeprazol, 5-OH-omeprazol, midazolam, metoprolol, ?-OHmetoprolol (método 2) e cafeína (método 3). Os métodos não apresentaram efeito matriz ou efeito residual e mostraram-se lineares para os analitos nos intervalos de 0,05-20 ng/mL (fexofenadina); 0,03 - 5 ng/mL (losartana e E31-74); 0,1 - 50 ng/mL (omeprazol), 0,3 - 50 ng/mL (5-OH-omeprazol), 0,01 - 10 ng/mL (midazolam), 0,05 - 50 ng/mL (metoprolol e ?- OH-metoprolol) e 5 - 1000 ng/mL (cafeína). Os parâmetros farmacocinéticos dos compostos foram calculados com base nas curvas de concentração plasmática versus tempo (AUC) empregando o programa Phoenix® WinNonlin®. Os valores das razões das AUC0-t e Cmax após e antes da exposição ao EPP-AF®, apresentados como média geométrica (IC90%) foram de 0,74 (0,62 - 0,89) e 0,90 (0,76 - 1,07) para fexofenadina; 0,88 (0,80 - 0,97) e 0,86 (0,76 - 0,98) para losartana; 0,96 (0,83 - 1,11) e 0,91 (0,79 - 1,04) para E-3174; 1,18 (0,91 - 1,54) e 1,21 (0,87- 1,70) para omeprazol; 1,12 (0,95 - 1,31) e 1,22 (0,95 - 1,67) para 5-OHomeprazol; 1,14 (1,03 - 1,28) e 1,21 (1,00 - 1,46) para o midazolam; 1,04 (0,92 - 1,18) e 0,94 (0,80 - 1,12) para o metoprolol; 1,05 (0,99 - 1,12) e 0,99 (0,88 - 1,12) para ?-OH-metoprolol; 0,97 (0,77 - 1,21) e 0,87 (0,69 - 1,11) para a cafeína. Quando observadas as razões metabólicas das AUC0-t E3174/losartana, 5-OH-omeprazol/omeprazol e ?-OHmetoprolol/ metoprolol encontramos, respectivamente, 1,11 (0,98 - 1,25); 0,94 (0,81 - 1,10) e 1,01 (0,88 - 1,16), indicando que, com exceção do CYP2D6, a administração de EPP-AF® nas condições estudadas apresenta potencial para inibição das isoformas CYP2C19 e CYP3A4 e indução das enzimas CYP1A2, CYP2C9 e do transportador de efluxo P-gp, embora as suas magnitudes encontram-se abaixo dos limites definidos pelos órgãos reguladores e portanto não apresentam relevância clínica / EPP-AF® is a standardized extract of propolis chemically characterized and with established pre-clinical efficacy and safety. The main objective of this work was to perform a clinical trial to evaluate the effect of EPP-AF® on P-gp and the major CYP isoforms activity, through an in vivo assay using the cocktail approach with sub-therapeutic doses. Sixteen healthy adult volunteers were investigated before and after exposure to orally administered 375 mg/day of EPP-AF® for 15 days. Serum blood samples were collected up to 12 h after the administration of midazolam (0.2 mg), caffeine (10 mg), omeprazole (2 mg), metoprolol (10 mg), losartan (2 mg) and fexofenadine (10 mg). Three analytical methods were developed and validated applying LC-MS/MS to quantify plasma concentrations of fexofenadine, losartan, E-3174 (method 1), omeprazole, 5-OH-omeprazole, midazolam, metoprolol, ?-OH-metoprolol (method 2), and caffeine (Method 3). Neither matrix effect nor carryover effect were observed. The methods were linear for the analytes in the ranges of 0.05 - 20 ng/mL (fexofenadine); 0.03 - 5 ng/ml (losartan and E-3174); 0.1 - 50 ng/mL (omeprazole), 0.3 - 50 ng/mL (5-OH-omeprazole), 0.01 - 10 ng/mL (midazolam), 0.05 - 50 ng/mL (metoprolol and ?-OH-metoprolol) and 5 - 1000 ng/mL (caffeine). The pharmacokinetic parameters of the compounds were calculated based on plasma concentration versus time (AUC) curves applying Phoenix® WinNonlin® software. AUC0-t and Cmax ratios after and before the EPPAF ® exposure, presented as geometric mean (CI 90%) were 0.74 (0.62 - 0.89) and 0.90 (0.76 - 1.07) for fexofenadine, 0.88 (0.80 - 0.97) and 0.86 (0.76 - 0.98) for losartan, 0.96 (0.83 - 1.11) and 0.91 (0.79 - 1.04) for E-3174, 1.18 (0.91 - 1.54) and 1.21 (0.87 - 1.70) for omeprazole; 1.12 (0.95 - 1.31) and 1.22 (0.95 - 1.67) for 5-OH-omeprazole, 1.14 (1.03 - 1.28) and 1.21 (1.00 - 1.46) for midazolam, 1.04 (0.92 - 1.18) and 0.94 (0.80 - 1.12) for metoprolol, 1.05 (0.99 - 1.12) and 0.99 (0.88 - 1.12) for ?-OH-metoprolol, 0.97 (0.77 - 1.21) and 0.87 (0.69 - 1.11) for caffeine. AUC0-t metabolic ratios of E3174/losartan, 5-OH-omeprazole/omeprazole and ?-OH-metoprolol/metoprolol we found to be, respectively, 1.11 (0.98 - 1.25), 0.94 (0.81 - 1.10 ) and 1.01 (0.88 - 1.16), indicating that, with the exception of CYP2D6, the administration of EPP-AF® under the conditions studied shows potential for CYP2C19 and CYP3A4 inhibition and CYP1A2, CYP2C9 and P-gp induction, although their magnitudes are below the limits defined by the regulatory agencies and therefore exhibit no clinical relevance