Srpski arhiv za celokupno lekarstvo 2015 Volume 143, Issue 1-2, Pages: 50-55
https://doi.org/10.2298/SARH1502050T
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Estimation of angiotensin-converting enzyme inhibitors protein binding degree using chromatographic hydrophobicity data
Trbojević-Stanković Jasna (Clinical Center “Dr Dragiša Mišović”, Clinic of Urology, Department of Hemodialysis, Belgrade)
Aleksić Mirjana (Faculty of Pharmacy, Department of Analytical Chemistry, Belgrade)
Odović Jadranka (Faculty of Pharmacy, Department of Analytical Chemistry, Belgrade)
Introduction. Angiotensin-converting enzyme (ACE) inhibitors represent a
significant group of drugs primarily used in the treatment of hypertension
and congestive heart failure. Objective. Selected ACE inhibitors (enalapril,
quinapril, fosinopril, lisinopril, cilazapril) were studied in order to
establish a fast and easy estimation method of their plasma protein binding
degree based on their lipophilicity data. Methods. Chromatographic
hydrophobicity data (parameter C0) were obtained on cellulose layers under
conditions of normal-phase thin-layer chromatography (NPTLC), using different
binary solvent systems. The ACE inhibitors lipophilicity descriptors (logP)
values were calculated using the software package Virtual Computational
Chemistry Laboratory. The ACE inhibitors plasma protein binding data were
collected from relevant literature. Results. ACE inhibitors protein binding
data varied from negligible (lisinopril) to 99% (fosinopril). The calculated
lipophilicity descriptors, logPKOWWIN values ranged from -0.94 (lisinopril)
to 6.61 (fosinopril). Good correlations were established between plasma
protein binding values and calculated logPKOWWIN values (R2=0.8026) as well
as chromatographic hydrophobicity data, C0 parameters (R2=0.7662). Even
though good correlation coefficients (R2) were obtained in both relations,
unacceptable probability value with p>0.05 was found in relation between
protein binding data and calculated logPKOWWIN values. Subsequently, taking
into consideration the request for probability value lower than 0.05, a
better relationship was observed between protein binding data and
chromatographically obtained hydrophobicity parameters C0 values. Conclusion.
Cellulose layers are easily available and cost effective sorbent to assess
hydrophobicity. Experimentally obtained data on ACE inhibitors hydrophobicity
and plasma protein binding estimation are important parameters in evaluating
bioavailability of these drugs.
Keywords: angiotensin-converting enzyme inhibitors, plasma protein binding, hydrophobicity
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