International Journal of Clinical Pharmacy

, Volume 39, Issue 5, pp 1095–1100 | Cite as

Adherence with perindopril therapy: a pilot study using therapeutic drug monitoring of perindoprilat and an evaluation of the clearance estimation

  • Martin ŠímaEmail author
  • Martin Vodička
  • Věra Marešová
  • Tomáš Šálek
  • Radomír Čabala
  • Ondřej Slanař
Research Article


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.


ACE inhibitors Compliance Creatinine Cystatin C Perindopril Therapeutic drug monitoring 



We thank Dr. Natasa Lekic for English language editing.


This work was supported by the Charles University Project Progres Q25 and a grant No. SVV 260373.

Conflicts of interest

The authors declare that there are no conflicts of interest regarding of this paper.


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Copyright information

© Springer International Publishing AG 2017

Authors and Affiliations

  1. 1.Department of Pharmacology, First Faculty of MedicineCharles University and General University Hospital in PraguePragueCzech Republic
  2. 2.Department of PharmacyTomas Bata Regional HospitalZlínCzech Republic
  3. 3.Institute of Forensic Medicine and Toxicology, First Faculty of MedicineCharles University and General University Hospital in PraguePragueCzech Republic
  4. 4.Department of Clinical Biochemistry and PharmacologyTomas Bata Regional HospitalZlínCzech Republic

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