Estimation of plasma protein binding of selected antipsychotics using computed molecular properties

Authors

  • Jelena D. Berić Faculty of Medical Science, University of Kragujevac, Kragujevac
  • Ratomir M. Jelić Faculty of Medical Science, University of Kragujevac, Kragujevac
  • Dejan M. Nešić Institute of Medical Physiology, School of Medicine, University of Belgrade, Belgrade
  • Jasna B. Trbojević-Stanković Department of Dialysis, Clinical Hospital Center "Dr Dragiša Mišović", School of Medicine, University of Belgrade, Belgrade
  • Jadranka V. Odović Department of Analytical Chemistry, University of Belgrade-Faculty of Pharmacy, Belgrade

Keywords:

antipsychotics, molecular descriptors, molecular properties, plasma protein binding

Abstract

The plasma protein binding (PPB) data of twelve antipsychotics (aripiprazole, clozapine, olanzapine, quetiapine, risperidone, sertindole, ziprasidone, chlorpromazine, flupentixol, fluphenazine, haloperidol, zuclopenthixol) were estimated using computed molecular descriptors, which included the electronic descriptor – polar surface area (PSA), the constitutional parameter – molecular weight (Mw), the geometric descriptor – volume value (Vol), the lipophilicity descriptor (logP) and aqueous solubility data (logS), and the acidity descriptor (pKa). The relationships between computed molecular properties of the selected antipsychotics and their PPB data were investigated by simple linear regression analysis. Low correlations were obtained between the PPB data of the antipsychotics and PSA, Mw, Vol, pKa, logS (R<0.30) values, while relatively higher correlations (0.35<R2<0.70) were obtained for the majority of logP values. Multiple linear regression (MLR) analysis was applied to access reliable correlations of the PPB data of the antipsychotics and the computed molecular descriptors. Relationships with acceptable probability values (P<0.05) were established for five lipophilicity descriptors (logP values) with application of the acidity descriptor (pKa) as independent variables: AlogP (R2=0.705), XlogP3 (R2=0.679), ClogP (R2=0.590), XlogP2 (R2=0.567), as well as for the experimental lipophilicity parameter, logPexp (R2=0.635). The best correlations obtained in MLR using AlogP and pKa as independent variables were checked using three additional antipsychotics: loxapine, sulpiride and amisulpride, with the PPB values of 97%, “less than” 40% and 17%, respectively. Their predicted PPB values were relatively close to the literature data. The proposed technique confirmed that lipophilicity, together with acidity significantly influences the PPB of antipsychotics. The described procedure can be regarded as an additional in vitro approach to the modeling of the investigated group of drugs.

https://doi.org/10.2298/ABS160912121B

Received: September 12, 2016; Revised: October 11, 2016; Accepted: October 12, 2016; Published online: November 4, 2016

How to cite: Berić JD, Jelić RM, Nešić DM, Trbojević-Stanković JB, Odović JV. Estimation of plasma protein binding of selected antipsychotics using computed molecular properties. Arch Biol Sci. 2017;69(3):463-8.

Downloads

Download data is not yet available.

References

Lemke TL, Williams DA.The Foye's Principles of Medicinal Chemistry, 7th ed. Philadelphia: Lippincott Williams & Wilkins; 2013. 1377 p.

Moffat AC, Osselton MD, Widdop B. Clarke’s Analysis of Drugs and Poisons. 4th ed. London: Pharmaceutical Press; 2011. 1500 p.

Rang HP, Ritter JM, Flower RJ, Henderson G. Rang and Dale’s Farmacology. 8th ed. Churchill Livingstone: Elsevier; 2012. 625 p.

Jašović Gašić M, Vuković O, Pantović M, Cvetić T, Marić Bojović N. Antipsychotics – History of development and field of indication, new wine – old glasses. Psychiatr Danub. 2012;24(Suppl. 3):342-4.

Seeman P, Lee T. Antipsychotic drugs: direct correlation between clinical potency and presynaptic action on dopamine neurons. Science. 1975;188(4194):1217-9.

Di L, Kernsy EH. Profiling drug – like properties in discovery research. Curr Opin Chem Biol. 2003;7:402-8.

Brunton LL, Chabner BA, Knollmann BC. Goodman and Gilman's: The Pharmacological Basis of Therapeutics. 12th ed. New York: The McGraw-Hill Companies, Inc.; 2011. 2084 p.

Hartmann T, Schmitt J. Lipophilicity – beyond octanol/water: a short comparison of modern technologies. Drug Discov Today Techn. 2004;1(4):431-9.

Remko M, Swart M, Bickelhaupt MF. Theoretical study of structure, pKa, lipophilicity, solubility, absorption and polar surface area of some centrally acting antihypertensives. Bioorg Med Chem. 2006;14:1715-28.

Remko M. Acidity, lipophilicity, solubility, absorption, and polar surface area of some ACE inhibitors. Chem. Pap. 2007;61(2):133-41.

Zhao YH, Le J, Abraham MH, Hersey A, Eddershaw PJ, Luscombe CN, Boutina D, Beck G, Sherbone B, Cooper I, Platts JA. Evaluation of human intestinal absorption data and subsequent derivation of a quantitative structure-activity relationship (QSAR) with the Abraham descriptors. J Pharm Sci. 2001;90:749-84.

Lipinski CA. Drug-like properties and the causes of poor solubility and poor permeability. J Pharmacol Toxicol Met. 2000;44:235-49.

Reddy VP, Kozielska M, Suleiman AA, Johnson M, Vermeulen A, Liu J, Greef R, Groothuis GMM, Danhof M, Proost JH. Pharmacokinetic-pharmacodynamic modelling of antipsychotic drugs in patients with schizophrenia: Part II: The use of subscales of the PANSS score. Schizophr Res. 2013;144:153-61.

Mauri MC, Volonteri LS, Colasanti A, Fiorentini A, De Gaspari IF, Bereggi SR. Clinical pharmacokinetics of atypical antipsychotics: a critical review of the relationship between plasma concentrations and clinical response. Clin Pharmacokinet. 2007;46(5):359-88.

Mauri MC, Paletta S, Maffini M, Colasanti A, Dragogna F, Di Pace C, Altamura AC. Clinical pharmacology of atypical antipsychotics: an update. EXCLI Journal. 2014;13:1163-91.

Odovic J, Trbojevic-Stankovic J. Correlation between Angiotensin-converting enzyme inhibitors lipophilicity and protein binding data. Acta Medica Medianae. 2012;51(4):13-8.

Trbojević J, Jelić M, Trbojević-Stanković J, Nešić D, Odović J. The estimation of relationship between calcium channel blockers’ molecular properties and plasma protein binding data. Arch Biol Sci. 2016;DOI:10.2298/ABS160609094O.

Odović J, Trbojević-Stanković J. In silico evaluation of angiotensin II receptor antagonist’s plasma protein binding using computed molecular descriptors. Acta Medica Medianae. 2014;53(1):19-24.

Odovic J, Markovic B, Vladimirov S, Karljikovic-Rajic K. In Vitro modeling of angiotensin-converting enzyme inhibitor's absorption with chromatographic retention data and selected molecular descriptors. J Chromatogr B. 2014;953:102-7.

Trbojević J, Odović J, Trbojević-Stanković J, Nešić D, Jelić R. The relationship between angiotensin II receptor antagonists’ bioavailability and molecular properties. Arch Biol Sci. 2016;68(2):273-8.

Trbojević - Stanković J, Odović J, Jelić R, Nešić D, Stojimirović B. The influence of certain molecular descriptors of fecal elimination of angiotensin II receptor antagonists. Arch Biol Sci. 2015;67(1):103-9.

Asuero AG, Sayago A, Gonzalez AG. The correlation coefficient: An overview. Crit Rev Anal Chem. 2006;36:41-59.

Kaitin KI. Obstacles and opportunities in new drug development. Clin Pharmacol Ther. 2008;83:210-2.

Mahanthappa M, Gowda BG, Gowda JI, Rengaswamy R. Spectroscopic, voltammetry and molecular docking study of binding interaction of antipsychotic drug with bovine serum albumin. J Electrochem Sci Eng. 2016;6(2):155-64.

Mannens G, Meuldermans W, Snoeck E, Heykants J. Plasma protein binding of risperidone and its distribution in blood. Psychopharmacology. 1994;114(4):566-72.

Stojanović S, Janković S, Matović Z, Jakovljević I, Jelić R. Interaction between tigecycline and human serum albumin in aqueous solution. Monatsh Chem. 2015;146:399-409.

Mannhold R, Poda GI, Tetko I. Calculation of molecular lipophilicity: state-of-the-art and comparison of log P methods on more than 96,000 compounds. J Pharm Sci. 2009;98:861-93.

Downloads

Published

2017-08-11

How to Cite

1.
Berić JD, Jelić RM, Nešić DM, Trbojević-Stanković JB, Odović JV. Estimation of plasma protein binding of selected antipsychotics using computed molecular properties. Arch Biol Sci [Internet]. 2017Aug.11 [cited 2024Mar.29];69(3):463-8. Available from: https://www.serbiosoc.org.rs/arch/index.php/abs/article/view/1003

Issue

Section

Articles

Most read articles by the same author(s)