Background Although measurement of drug serum levels is an objective direct method for testing compliance, it can be distorted by "white-coat compliance" or by variations in drug elimination. Objective The aim of this prospective study was to evaluate the prevalence of noncompliance with perindopril therapy in adult out-patients using pharmacokinetic simulations. The additional aim was to compare the predictive performance of two glomerular filtration rate markers-creatinine and cystatin C. Setting Department of Cardiology, Tomas Bata Regional Hospital in Zlín, Czech Republic. Method Perindoprilat pharmacokinetic models individualized according to patient characteristics were compared with measured perindoprilat serum concentrations to document compliance. Linear regression was used to evaluate the relations between perindoprilat clearance and glomerular filtration rate estimated using creatinine and cystatin C. Main outcome measure Assessment of non-compliance with medication using drug concentration measurements reinforced with therapeutic drug monitoring. Results Non-detectable perindoprilat levels were observed in 26.1% of patients. Another 21.7% were classified as non-compliant based on therapeutic drug monitoring pharmacokinetic simulations. Volume of distribution, clearance and half-life median value (interquarti°range) for perindoprilat were 408.3 (360.4-456.8) L, 10.1 (4.9-17.0) L h-1 and 24.7 (19.4-62.7) h, respectively. Linear regression models showed tight relationship between cystatin C and perindoprilat clearance. Conclusions Assessment of adherence with medication reinforced with therapeutic drug monitoring and pharmacokinetic simulations is proposed as an optimal method reducing disadvantages of simple drug concentration measurements. Cystatin C proves to be better surrogate marker for perindoprilat elimination than creatinine.
- Klíčová slova
- ACE inhibitors, Compliance, Creatinine, Cystatin C, Perindopril, Therapeutic drug monitoring,
- MeSH
- adherence k farmakoterapii * MeSH
- cystatin C metabolismus MeSH
- hodnoty glomerulární filtrace účinky léků fyziologie MeSH
- inhibitory ACE metabolismus farmakologie MeSH
- kreatinin metabolismus MeSH
- lidé MeSH
- metabolická clearance účinky léků fyziologie MeSH
- monitorování léčiv metody MeSH
- perindopril metabolismus farmakologie MeSH
- pilotní projekty MeSH
- prospektivní studie MeSH
- senioři MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- klinické zkoušky MeSH
- Názvy látek
- cystatin C MeSH
- inhibitory ACE MeSH
- kreatinin MeSH
- perindopril MeSH
Transforming growth factor (TGF)-beta is believed to play a key role in the development of many autoimmune and malignant diseases, such as radiation and drug-induced organ disease. The aim of the present study was to determine messenger RNA (mRNA) production of TGF-beta 1 in the lungs of C57Bl6 mice after low-dose whole-body irradiation. Control (irradiated) and irradiated angiotensin-converting enzyme (ACE) inhibitor-treated animals were simultaneously examined. The ACE inhibitor group received butylaminiperindopril for 9 days after irradiation (7 Gy) at a daily dose of 0.1 mg/kg per rectum. On day 9 all mice were sacrificed and the production of mRNA TGF-beta 1 in lung tissue was determined semiquantitatively using reverse transcriptase polymerase chain reaction. In butylaminiperindopril-treated mice, a decrease in transcript of TGF-beta 1 (to 59% in comparison with controls) was observed.
- MeSH
- celotělové ozáření * MeSH
- inhibitory ACE farmakologie MeSH
- kaptopril farmakologie MeSH
- messenger RNA biosyntéza MeSH
- myši inbrední C57BL MeSH
- myši MeSH
- perindopril analogy a deriváty farmakologie MeSH
- plíce účinky léků metabolismus účinky záření MeSH
- polymerázová řetězová reakce s reverzní transkripcí MeSH
- transformující růstový faktor beta genetika MeSH
- volné radikály MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- inhibitory ACE MeSH
- kaptopril MeSH
- messenger RNA MeSH
- perindopril MeSH
- transformující růstový faktor beta MeSH
- volné radikály MeSH
