AIM: The aim of this study was to evaluate adherence to spironolactone in a group of unselected patients with arterial hypertension by analysis of measured serum spironolactone and canrenone concentrations according to a proposed two-step decision scheme based on pharmacokinetic considerations. MATERIALS AND METHODS: Simulation of serum concentration-time profiles of spironolactone and canrenone based on population pharmacokinetic parameters described in literature and a body weight-normalized spironolactone dose / canrenone level nomogram derived from a group of adherent patients with conservatively treated primary hyperaldosteronism, were used to create a two-step decision scheme. 71 outpatients treated with spironolactone for resistant hypertension with spironolactone and canrenone serum concentrations measured between 2018 and 2021 were analyzed according to the proposed scheme. We compared our proposed methodology to the standard approach for adherence testing. RESULTS: With the most sensitive traditional approach to adherence assessment through detectable serum concentrations of spironolactone and/or canrenone, 9 (12.7%) non-adherent patients were identified. With our two-step assessment of adherence, we were able to identify 18 (25.4%) non-adherent patients. CONCLUSION: Consideration of the pharmacokinetic properties of parental drug and its metabolite led to improved sensitivity in non-adherence detection in patients with arterial hypertension. This approach enables better interpretation of measured spironolactone and canrenone serum concentrations and should be used in clinical practice.

• MeSH
• adherence k farmakoterapii * MeSH
• antagonisté mineralokortikoidních receptorů farmakokinetika   MeSH
• dospělí MeSH
• hyperaldosteronismus farmakoterapie   krev   MeSH
• hypertenze * farmakoterapie   MeSH
• kanrenon * farmakokinetika   MeSH
• lidé středního věku MeSH
• lidé MeSH
• pilotní projekty MeSH
• senioři MeSH
• spironolakton * farmakokinetika   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

Mycophenolate mofetil (MMF) is an immunosuppressant drug approved for prophylaxis of transplant rejection in patients undergoing solid organ transplantation and is further employed in management of various autoimmune disorders. MMF exhibits notable pharmacokinetic inter- and intraindividual variability necessitating tailored therapeutic approaches to achieve optimal therapeutic outcomes while mitigating risks of adverse effects. The objective of this review was to summarize factors that influence the pharmacokinetics of MMF and its active metabolite mycophenolic acid in order to deduce recommendations for personalized treatment strategies. Presumed predictors were analysed in relation to each of the four pharmacokinetic phases, providing tools and targets for MMF dosing optimization amenable to clinical implementation.

• MeSH
• imunosupresiva * farmakokinetika   aplikace a dávkování   MeSH
• individualizovaná medicína MeSH
• kyselina mykofenolová * farmakokinetika   aplikace a dávkování   MeSH
• lidé MeSH
• rejekce štěpu prevence a kontrola   MeSH
• transplantace orgánů * MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

V důsledku obezity dochází ke změnám farmakokinetických parametrů a hladin podávaných léků v krvi, což může významně komplikovat farmakoterapii obézních pacientů. Zpravidla dochází ke zvětšování distribučního objemu, tyto změny však nejsou vždy přímo úměrné nárůstu celkové tělesné hmotnosti, uplatňuje se relativní zvýšení množství tukové hmoty oproti hydrofilnímu kompartmentu. Vlivem obezity mohou být ovlivněny i eliminační orgány, což vede ke změnám clearance léčiv. Prosté navýšení dávek podle celkové tělesné hmotnosti by u mnohých pacientů mohlo vést k předávkování, naopak fixní dávky mohou být spojeny s nedostatečným efektem. Změny tělesného složení a eliminace se však u různých léčiv neprojeví stejným způsobem. Nelze tedy jednoznačně určit univerzální postup úpravy dávek pro všechna léčiva. Specifickou problematikou je dávkování léčiv po bariatrických operacích, kdy je nutné zohlednit jak změny biodostupnosti a jejich postupnou úpravu v čase od výkonu, tak dramatickou redukci hmotnosti vyžadující pravidelné přehodnocování farmakoterapie. Přestože je obezita celosvětově narůstajícím problémem, stále se potýkáme s nedostatečným množstvím spolehlivých dat a klinických studií zabývajících se problematikou dávkování léčiv u obézních pacientů. Předložený článek uvádí na základě dostupných informací základní principy dávkování u obézních pacientů.

Obesity is related to changes in pharmacokinetic parameters and blood levels of administered drugs, which can significantly complicate the pharmacotherapy of obese patients. An increase in the volume of distribution is generally expected, but due to a relative increase in the amount of fat mass compared to the hydrophilic compartment, this change is not always directly proportional to the increase in total body weight. The elimination organs may also be affected by obesity, leading to changes in drug clearance. Simply increasing doses according to total body weight could lead to overdose in many patients, whereas fixed doses may be associated with insufficient therapeutic effect. However, changes in body composition and elimination are not consistent for different drugs. Therefore, an unambiguous recommendation for dose adjustment of all drugs cannot be made. Drug dosing after bariatric surgery presents a unique challenge, when it is necessary to assess changes in bioavailability and their gradual adjustment over time from the procedure, as well as dramatic weight reduction requiring regular reassessment of pharmacotherapy. Although obesity is a growing problem worldwide, we still face an insufficient amount of reliable data and clinical studies dealing with drug dosing in obese patients. Based on the available information, this article describes the basic principles of dosing in obesity.

• Klíčová slova
• dávkování léků, distribuční objem, úpravy dávek,
• MeSH
• farmakokinetika * MeSH
• lidé MeSH
• obezita * MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• práce podpořená grantem MeSH
• přehledy MeSH

Polypragmazie je v současné době závažný problém, který je spojen nejen se snížením adherence, ale i s častější hospitalizací a vyšší mortalitou. Intervenci, které by výskyt polypragmazie omezily, se věnuje WHO v rámci kampaně Medication Without Harm, ale i různé iniciativy, jako Mezinárodní skupina pro omezení použití nevhodných léčiv a polypragmazie (IGRIMUP) nebo kampaň Choosing Wisely. Správný přístup k řešení polypragmazie spočívá v prevenci, tedy nepředepisování zbytných léčiv a časovém omezení léčby, pokud není zamýšlena jako celoživotní. Dále v cíleném vyhledávání pacientů s polypragmazií a v cílené intervenci pomocí tzv. depreskripce. Pro správné a uvážené vedení depreskripce je dostupná řada postupů, od seznamů nevhodných léčiv (Beersova kritéria, STOPP/START ad.) po komplexní metody vyhodnocování významu jednotlivých léků v medikaci pacienta, pomocí kterých lze vyhledat nejvhodnější kandidáty k depreskripci (index vhodnosti léků, algoritmus dobré paliativní geriatrické praxe a mnohé další). V rámci hodnocení účinnosti farmakoterapie vždy ověřujeme, zda je dosaženo účinku, pro který je lék předepsán, zda indikace trvá v čase, kontrolujeme dávkování a také, zda pacient léčbu chápe. Tím se snažíme eliminovat farmakoterapii s velice malým či žádným benefitem pro konkrétního pacienta. S tímto relativně časově náročným procesem může významně pomoci klinický farmaceut nebo farmakolog.

Polypharmacy is currently a serious problem that causes decrease in adherence and increased number of hospitalizations and mortality. WHO addresses polypharmacy in the Medication Without Harm campaign. Other initiatives that deal with polypharmacy are the International Group for Reducing Inappropriate Medication Use & Polypharmacy (IGRIMUP) and Choosing Wisely campaign. The correct approach to address polypharmacy consists of its prevention, i.e. not prescribing inappropriate or unnecessary medication and providing clear timeframe for medication that should not be continued life-long. Further on we should actively seek patients suffering from polypharmacy and intervene it by deprescription. Correctly provided deprescription can be done by means of various tools beginning from simple lists of inappropriate drugs (Beers criteria, STOPP/START) to more comprehensive approaches that evaluate the importance of each particular drug in patient’s medication list and help to identify the least important ones that are candidates for deprescription (Medication Appropriateness Index, Good Palliative Geriatric Practice Algorithm and others). When evaluating the appropriateness of pharmacotherapy, we always check if the treatment aim is achieved, if the indication persists, appropriateness of dosing and if the patient understands the pharmacotherapeutical regimen. By this approach we try to eliminate the pharmacotherapy with very low or no benefit for particular patient. Clinical pharmacologist or pharmacist can significantly help with this time-consuming process.

• MeSH
• depreskripce MeSH
• lidé MeSH
• nadužívání zdravotní péče MeSH
• polypharmacy * prevence a kontrola   MeSH
• senioři MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• Publikační typ
• kazuistiky MeSH
• přehledy MeSH

• Publikační typ
• abstrakt z konference MeSH

• Publikační typ
• abstrakt z konference MeSH

• Publikační typ
• abstrakt z konference MeSH

BACKGROUND: Amikacin monotherapy is recommended for urinary tract infection (UTI) treatment with multi-resistant pathogens. Even though amikacin efficacy in the treatment of UTIs is dependent on its urinary concentration, there are no robust data proving that sufficiently high urinary concentration is reached in patients with reduced glomerular filtration rate (GFR). METHODS: A prospective study to monitor amikacin penetration into urine of 70 patients [40 males, median (interquartile range) age 70 (65-79) years] with different levels of glomerular filtration decline, including patients treated by dialysis, was conducted. The bactericidal efficacy of amikacin in urine samples has been evaluated. RESULTS: Patients with estimated GFR (eGFR) <30 mL/min had significantly lower median amikacin urinary concentration than patients with eGFR >30 mL/min (89.75 vs 186.0 mg/L, P < .0001; 200.5 vs 830.0 mg/L, P < .0001; and 126.0 vs 408.0 mg/L, P < .0001 for minimal, maximal and minimal together with maximal concentrations, respectively). The amount of amikacin eliminated in the first 10-13 h after dose administration was dependent on eGFR (r2 = 0.6144, P < .0001). The urinary concentration of amikacin in patients treated by dialysis was indirectly proportional to pH of urine. The plasma concentrations of amikacin did not correlate with urinary levels in patients in either of the GFR categories. Microbiological evaluation showed that the critical urinary concentration for efficacy of amikacin during UTI monotherapy in patients treated by dialysis is 100 mg/L. We found that 4 out of 11 patients treated by dialysis did not reach this level during the treatment. CONCLUSION: Systemic administration of amikacin monotherapy in patients treated by dialysis is questionable as the concentrations of amikacin in their urine are often below the threshold of effectivity. Amikacin plasma concentrations are not a major determinant of amikacin concentration in urine, therefore pulse dosing is neither necessary nor safe in patients treated by dialysis, and may cause undesirable toxicity.

• Publikační typ
• časopisecké články MeSH

PURPOSE OF REVIEW: Oral drug absorption after bariatric surgery is likely to be altered, but the impact of different bariatric surgery procedures on individual drugs is not uniform. The aim of this article is to describe factors influencing the bioavailability of orally administered drugs after bariatric surgery and to provide readers with practical recommendations for drug dosing. We also discuss the medications that may be harmful after bariatric surgery. RECENT FINDINGS: The fundamental factors for enteral drug absorption are the production of gastric acid; the preserved length of the intestine, i.e., the size of the absorption surface and/or the preserved enterohepatic circulation; and the length of common loop where food and drugs are mixed with digestive enzymes and bile acids. Bypassing of metabolizing enzymes or efflux pumps and changes in intestinal motility can also play an important role. Significant changes of drug absorption early after the anatomic alteration may also be gradually ameliorated due to gradual intestinal adaptation. The most affected drugs are those with low or variable bioavailability and those undergoing enterohepatic circulation. Attention should also be paid to oral drug formulations, especially in the early postoperative period, when immediate-release and liquid formulations are preferred. The changes in oral bioavailability are especially clinically meaningful in patients treated with drugs possessing narrow therapeutic index (e.g., oral anticoagulants, levothyroxine, and anticonvulsants) or in acute conditions (e.g., anti-infectives); nevertheless, it may also influence the therapeutic value of chronic therapy (e.g., antidepressants. antihypertensives, antiplatelets, statins, PPIs, contraceptives, and analgesics); therapeutic effect of chronic therapy is further influenced by pharmacokinetic alterations resulting from weight loss. Therapeutic drug monitoring, periodical clinical evaluation, and adequate dose adjustments are necessary. Due to safety reasons, patients should avoid oral bisphosphonates, regular use of non-steroidal anti-inflammatory drugs, and, if possible, corticosteroids after bariatric surgery.

• MeSH
• bariatrická chirurgie * metody   MeSH
• biologická dostupnost MeSH
• gastrektomie MeSH
• hmotnostní úbytek MeSH
• lidé MeSH
• morbidní obezita * chirurgie   MeSH
• žaludeční bypass * MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

Immunoglobulin A nephropathy (IgAN) is the most common primary glomerulonephritis worldwide, with a potentially serious prognosis. At present, management of IgAN is primarily based on therapeutic lifestyle changes, and excellent blood pressure control and maximized supportive treatment with the combination of inhibition of the renin-angiotensin-aldosterone system with either inhibitors of angiotensin-converting enzyme or angiotensin II receptor blockers and inhibitors of sodium-glucose cotransporter-2, and possibly in the future also with endothelin antagonists. Supportive care currently represents the cornerstone of treatment of IgAN. Targeted-release formulation of budesonide should replace systemic corticosteroids in patients with higher proteinuria and active histological lesions. New treatment options are aimed at immunopathogenesis of IgAN including depletion or modulation of Galactose-deficient-Immunoglobulin A1-producing B cells, plasma cells, and the alternate and/or lectin pathway of complement. The exact place of monoclonal antibodies and complement inhibitors will need to be determined. This article reviews potential supportive therapies currently available for patients with IgAN.

• Publikační typ
• časopisecké články MeSH
• přehledy MeSH