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
OBJECTIVES: Rituximab is being increasingly prescribed for the treatment of autoimmune glomerular diseases. While it is highly effective for some diseases, the response is less predictable for others, which may be due to differing requirements in terms of the dosing according to the disease type and variations concerning exposure to the drug. METHODS: We compiled novel rituximab dosing schedules according to pharmacokinetic analysis of data gathered from rituximab treated patients in a tertiary referral nephrology centre between May 2020 and June 2023. The population-pharmacokinetic analysis was based on the rituximab dosing, the patients' characteristics, rituximab levels and anti-rituximab antibodies. RESULTS: The analysis, which was based on data from 185 patients, clearly highlighted differing rituximab dosing requirements for patients with ANCA associated vasculitis and minimal change disease compared to those with membranous nephropathy, focal-segmental glomerulosclerosis and lupus nephritis. This corresponded to the good treatment response of the first two diseases and the unreliable efficacy for the others. The model predicts the rituximab pharmacokinetics with high degree of accuracy when body weight, proteinuria, type of glomerulonephritis, treatment length and anti-rituximab antibodies formation are used as covariates. We proposed a dosing schedule with shortened dosing intervals for difficult-to-treat diagnoses with high proteinuria. CONCLUSION: In order to ensure reliable and comparable exposure of rituximab with respect to the full range of glomerular diseases, the dosing schedule should be adjusted for membranous nephropathy, focal-segmental glomerulosclerosis and lupus nephritis. This is largely, but not solely, due to the enhanced level of unselective proteinuria in these diseases.
- MeSH
- biologické modely MeSH
- dospělí MeSH
- glomerulonefritida farmakoterapie MeSH
- lidé středního věku MeSH
- lidé MeSH
- membranózní glomerulonefritida farmakoterapie MeSH
- mladý dospělý MeSH
- rituximab * farmakokinetika aplikace a dávkování terapeutické užití MeSH
- rozvrh dávkování léků MeSH
- senioři MeSH
- výsledek terapie MeSH
- vztah mezi dávkou a účinkem léčiva MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
Background: Ivacaftor is a modern drug used in the treatment of cystic fibrosis. It is highly lipophilic and exhibits a strong positive food effect. These characteristics can be potentially connected to a pronounced lymphatic transport after oral administration. Methods: A series of studies was conducted to describe the basic pharmacokinetic parameters of ivacaftor in jugular vein cannulated rats when dosed in two distinct formulations: an aqueous suspension and an oil solution. Additionally, an anesthetized mesenteric lymph duct cannulated rat model was studied to precisely assess the extent of lymphatic transport. Results: Mean ± SD ivacaftor oral bioavailability was 18.4 ± 3.2% and 16.2 ± 7.8%, respectively, when administered as an aqueous suspension and an oil solution. The relative contribution of the lymphatic transport to the overall bioavailability was 5.91 ± 1.61% and 4.35 ± 1.84%, respectively. Conclusion: Lymphatic transport plays only a minor role in the process of ivacaftor intestinal absorption, and other factors are, therefore, responsible for its pronounced positive food effect.
- Publikační typ
- časopisecké články 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
The objective of this prospective study was to examine the exposure to the main active metabolites of ciprofloxacin in critically ill patients and to examine the factors (demographic, laboratory and genetic) that could potentially affect the drug metabolic conversion of ciprofloxacin. The secondary aim was to develop a population pharmacokinetic model for the metabolite showing the most associations with the abovementioned factors. A total of 29 patients were treated with intravenous infusion of ciprofloxacin and enrolled on this trial. Blood samples for pharmacokinetic analysis were taken at 1, 4, and 11.5 h following the completion of the infusion. Sex, age, body weight, height, serum creatinine and bilirubin levels, and creatinine clearance (CLCR) were recorded, and polymorphisms rs2032582 and rs1045642 in the ABCB1 gene, rs4148977 in the SLCO1A2 gene and rs762551 in the CYP1A2 gene were analyzed. A three-stage parent drug-metabolite population pharmacokinetic model was developed. Median (IQR) metabolite/parent ratios of the desethylene ciprofloxacin, formyl ciprofloxacin and oxociprofloxacin were 5.86 (4.09-9.87)%, 4.08 (3.38-6.92)% and 5.91 (3.42-13.65)%, respectively. The desethylene ciprofloxacin metabolic ratio was positively associated with height (r2 = 0.2277, p = 0.0089) and CLCR (r2 = 0.2023, p = 0.0144) and negatively associated with age (r2 = 0.2227, p = 0.0112). Males had a significantly higher oxociprofloxacin metabolic ratio than females (9.14 vs 3.42%, p = 0.0043). In the desethylene ciprofloxacin population PK model, the volume of distribution decreased with age, the parent drug-metabolite transfer rate constant increased with CLCR, and the metabolite elimination rate constant decreased with age and is increased in CYP1A2 rs762551 variant allele carriers. We therefore hypothesized that the CYP1A2 inhibition by ciprofloxacin is mediated by its metabolite desethylene ciprofloxacin.
- Publikační typ
- časopisecké články MeSH
Od 60. let minulého století hraje hormonální antikoncepce důležitou roli v životě spousty mladých žen. I přesto, že správně indikovaná antikoncepce přispívá jak tělesnému, tak duševnímu zdraví žen a je pro mnoho z nich výbornou ochranou před neplánovaným těhotenstvím, je některými odmítána pro obavy, které ne vždy nalézají oporu v dnešní medicíně založené na důkazech. I hormonální antikoncepce má své nežádoucí účinky, a proto je nutná racionální diskuze s lékařem, aby bylo každé ženě umožněno učinit informované rozhodnutí o výběru ochrany před neplánovaným těhotenstvím.
Since the 1960s, hormonal contraception has played an important role in the lives of many young women. Despite the fact that properly indicated contraception contributes to both the physical and mental health of women and for many of them is an excellent protection against unplanned pregnancy, it is rejected by some because of concerns that are not always supported by today's evidence-based medicine. Even hormonal contraceptives have side effects a rational discussion with doctor is necessary to allow each woman to make an informed decision about her choice of protection from unplanned pregnancy.
Gynekomastie jako taková je častým nálezem v mužské populaci. Z údajů v literatuře se dá usuzovat, že léčivy vyvolanou gynekomastií trpí zhruba 3-16 % mužské populace. Efekt, jakým gynekomastii způsobují jednotlivá léčiva, není jednotný a u některých léčiv není ani dobře známý. Mezi léčivy, u kterých se vyskytuje gynekomastie jako nežádoucí účinek, nás nepřekvapí přítomnost řady hormonálních léčiv. Další látky, u nichž je dobře prokázána asociace s gynekomastií, jsou spironolakton, omeprazol, někteří zástupci blokátorů kalciových kanálů, antiretrovirotik či antipsychotik, ethanol a alkylační látky. Dále existuje řada léčiv, u kterých se o množném vztahu s gynekomastií hovoří, nicméně tento vztah nebyl jednoznačně prokázán.
Gynecomastia is a common finding in a male population. Regarding the literature we can estimate that approximately 3-16 % of male population has drug induced gynecomastia. Drugs are causing gynecomastia by variety of mechanisms, some of them are yet to be found. It is not surprising that among hormonal medications there are plenty of drugs with gynecomastia as an adverse effect. Other well-known drugs which can induce gynecomastia are spironolactone, omeprazole, some calcium channel blockers, some antiretroviral drugs, some antipsychotics, ethanol and alkylating agents. There are also lot of drugs which are speculated to cause a gynecomastia, however there is not enough evidence to support it.
