Clearance léčiva je parametr, díky němuž můžeme nastavit racionální dávkovací režim při dlouhodobé aplikaci léčiva. Informuje nás o efektivnosti eliminace léčiva, a to jak celkové, tak o eliminaci jednotlivými orgány. Různými mechanismy může docházet ke zvýšení či snížení clearance léčiva.
Clearance of a drug is a parameter which allows us to set rational dosing regimen for long‑term drug treatment. It informs us about the effectiveness of overall drug elimination and elimination by individual organs. Different mechanisms may lead to an increase or decrease of drug clearance.
- MeSH
- Renal Elimination * physiology immunology drug effects MeSH
- Pharmacokinetics MeSH
- Hepatobiliary Elimination * physiology immunology drug effects MeSH
- Glomerular Filtration Rate physiology immunology drug effects MeSH
- Pharmacology, Clinical methods standards trends MeSH
- Clinical Laboratory Techniques methods standards trends MeSH
- Kidney Tubules physiology physiopathology drug effects MeSH
- Humans MeSH
- Metabolic Clearance Rate * physiology immunology drug effects MeSH
- Renal Reabsorption physiology immunology drug effects MeSH
- Statistics as Topic MeSH
- Check Tag
- Humans MeSH
Pfii modelování kinetiky difuze a relaxace v polymerní matrici se nejãastûji vyuÏívá mocninná rovnice ve dvouparametrovém nebo tfiíparametrovém tvaru. V úvodní ãásti jsou shrnuty pouÏívané varianty mocninné rovnice vãetnû rovnice umoÏÀující rozli‰ení mezi difuzí a relaxací. Kinetika liberace pilokarpiniumchloridu z lyofilizovan ˘ch lamel s odstupÀovan˘m mnoÏstvím hydroxypropylmethylcelulosy je vyjádfiena mocninn˘mi rovnicemi a jsou srovnány jejich parametry. V závûru je diskutována pouÏitelnost mocninné rovnice pfii modelování liberace léãiv˘ch látek a doporuãeno vyuÏití tfiíparametrové mocninné rovnice s posunem uvolÀování mimo poãátek soufiadnic.
For the modelling of the kinetics of diffusion and relaxation in the polymer matrix, the power law equation in a two-parameter or three-parameter form is employed. The introductory part of the paper summarizes the employed varieties of the power law equation including the equation making it possible to distinguish diffusion from relaxation. The liberation kinetics of pilocarpinium chloride from lyophilized lamellae with graded amounts of hydroxypropylmethylcellulose is expressed by power law equations and their parameters are compared. The conclusion discusses the usability of the power law equation in the modelling of liberation of active ingredients and recommends the use of the three-parameter power law equation with a shift of the liberation out of the origin of the coordinates.
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.
- Keywords
- dávkování léků, distribuční objem, úpravy dávek,
- MeSH
- Pharmacokinetics * MeSH
- Humans MeSH
- Obesity * MeSH
- Check Tag
- Humans MeSH
- Publication type
- Research Support, Non-U.S. Gov't MeSH
- Review MeSH
[Paediatric clinical pharmacist: a potential benefit?]
Prevalence lékových pochybení v pediatrii se odhaduje na 10–15 % a téměř v polovině případů se dle publikované evidence jedná o nesprávné dávkování léčiva. Vzhledem ke značné vývojové variabilitě farmakokinetiky a/nebo farmakodynamiky parametrů dětských pacientů představují rizikovou skupinu pro léková pochybení především novorozenci a děti do 2 let věku a na druhé straně obézní děti, které mají parametry dospělého. Klinický farmaceut orientovaný v problematice je dalším prvkem v účelné a bezpečné farmakoterapii v komplexní péči napříč mnoha pediatrickými specializacemi.
Medication errors in paediatric prescribing occur in approximately 10-15 % cases, almost half of these errors are represented by incorrect drug dosing. Maturational changes in pharmacokinetics and/or pharmacodynamics parameters of paediatric patients across different paediatric categories represent a challenge to optimal drug prescribing. Especially neonatal and infant populations along with obese children of adult size are the most vulnerable groups prone to medication errors. Clinical pharmacist focused on paediatric pharmacotherapy verification is another element ensuring safe and rational medication use across different paediatric specialities.
- MeSH
- Pharmacokinetics MeSH
- Drug Therapy MeSH
- Pharmacology, Clinical * MeSH
- Humans MeSH
- Pediatrics * MeSH
- Check Tag
- Humans MeSH
- Publication type
- Review MeSH
Background. Cyclosporine A (CsA) is an immunomodulatory agent used in standard immunosuppressive regimens in solid organ transplantations as well as in the treatment of autoimmune diseases such as rheumatoid arthritis (RA), systemic lupus and psoriasis. Its immunosuppressive activity is primarily due to parent drug. However, following oral administration, absorption is incomplete and varies between individuals. Further, there is a dearth of pharmacokinetic data for CsA in autoimmune patients compared to transplant recipients. Aim. The goal of this study was to investigate the single-dose and steady state pharmacokinetics of CsA and two main primary metabolites, AM1 and AM4N, in patients with rheumatic/autoimmune diseases. Methods. Thirty-eight subjects, average age (years± SD) 46.8 (±11.6) years with rheumatoid arthritis, systemic lupus erythematosus, psoriatic arthritis, ankylosing spondylitis and undifferentiated SpA were included in an observational open study. The single dose pharmacokinetics (area under the concentration–time curve of CsA and its metabolites (AUC) and other PK parameters) were determined over a 24 h period following oral administration of 1.3 mg/kg oral CsA. Two CsA formulations-Neoral and the Czech generic substitute Consupren®, were used. Pharmacokinetic analysis was performed on all 38 patients after administration of a single dose of CsA (1.34 mg/ kg/day). In 12 patients only, a second series of blood samples was taken to calculate monitored PK parameters under steady state conditions. Results. Pharmacokinetic assessment showed AUC0-24 3009.66 ± 1449.78 ng/ml.h and Cmax 827.84 ± 425.84 after administration of a single dose of CSA, AUC0-24 3698.50 ± 2147 ng/ml.h and Cmax 741 ± 493 ng/ml after repeated dose. The proportion of the AM1 metabolite (AUC0-24) after a single dose of CsA corresponded to 40% of the parent compound and to approximately 35% of the parent compound in steady state conditions. The proportion of AM4N metabolite was low in both conditions and represented only 3 and 4.5% after a single dose and at steady state, respectively. Conclusion. The pharmacokinetic data (AUCCsA, Cmax) for the whole 24 h interval were similar to the published findings, mainly under steady state conditions. The AM1 (AUC0-24) after a single dose of CsA and in steady state conditions represented about 40% of the parent drug. The ratio of AM4N metabolite was low in both conditions.
- MeSH
- Autoimmune Diseases drug therapy immunology MeSH
- Cyclosporine administration & dosage pharmacokinetics metabolism MeSH
- Adult MeSH
- Pharmacokinetics MeSH
- Immunosuppressive Agents blood metabolism MeSH
- Middle Aged MeSH
- Humans MeSH
- Area Under Curve MeSH
- Arthritis, Rheumatoid drug therapy immunology MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
The concentration of a drug in the circulatory system is studied under two different elimination strategies. The first strategy--geometric elimination--is the classical one which assumes a constant elimination rate per cycle. The second strategy--Poisson elimination--assumes that the elimination rate changes during the process of elimination. The problem studied here is to find a relationship between the residence-time distribution and the cycle-time distribution for a given rule of elimination. While the presented model gives this relationship in terms of Laplace-Stieltjes transform., the aim here is to determine the shapes of the corresponding probability density functions. From experimental data, we expect positively skewed, gamma-like distributions for the residence time of the drug in the body. Also, as some elimination parameter in the model approaches a limit, the exponential distribution often arises. Therefore, we use Laguerre series expansions, which yield a parsimonious approximation of positively skewed probability densities that are close to a gamma distribution. The coefficients in the expansion are determined by the central moments, which can be obtained from experimental data or as a consequence of theoretical assumptions. The examples presented show that gamma-like densities arise for a diverse set of cycle-time distribution and under both elimination rules.
- MeSH
- Models, Biological * MeSH
- Pharmacokinetics * MeSH
- Humans MeSH
- Mathematics MeSH
- Metabolic Clearance Rate MeSH
- Stochastic Processes MeSH
- Check Tag
- Humans MeSH
- Publication type
- Research Support, Non-U.S. Gov't MeSH
