PREDICTION ANALYSIS OF PHARMACOKINETIC PARAMETERS OF SEVERAL ORAL SYSTEMIC DRUGS USING INSILICO METHOD
DOI:
https://doi.org/10.22159/ijap.2020.v12s1.FF057Keywords:
Absorption percentage, Absorption, distribution, metabolism, and excretion prediction, In silico, Oral systemic drugs, Physicochemical parameters, Pharmacokinetic parametersAbstract
Objective: This research aims to observe the pharmacokinetic parameters that can be predicted using a software, discover the best software to predict
pharmacokinetic properties, and analyze the correlation between pharmacokinetic parameters used as descriptors with absorption percentage
(%ABS) from references.
Methods: This research was conducted using Molinspiration, QikProp, admetSAR, SwissADME, Chemicalize, and pkCSM software. This research
analyzed 34 oral systemic drug compounds for absorption rate and six descriptors comprising molecular weight (MW), logP, hydrogen bond acceptor
(HBA), hydrogen bond donor (HBD), polar surface area (PSA), and pKa.
Results: SwissADME showed the most accurate prediction of MW, logP, and HBD. Chemicalize showed the most accurate prediction of HBA, PSA, and
pKa. Further, admetSAR showed the most accurate prediction of Caco-2 permeability. The highest R value was obtained from the correlation between
%ABS with Caco-2 permeability on 34 drug compounds (R=0.8211).
Conclusion: The highest R value was obtained from the correlation between %ABS with Caco2 permeability on 34 drug compounds (R=0.8211),
which showed a significant relationship (*p<0.001). This indicates that oral systemic drugs are affected by Caco-2 permeability. Moreover, the result of this research can be considered for the development of oral systemic drugs.
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References
Engman H. Intestinal barriers to oral drug absorption. Analysis
;9:1-62.
Song NN, Zhang S, Liu C. Overview of factors affecting oral drug
absorption. Asian J Drug Metab Pharmacokinet 2004;4:167-76.
Shargel L, Wu-Pong S, Yu A. Applied Biopharmaceutics and
Pharmacokinetics. Annals of Internal Medicine. 5th ed., Vol. 94.
New York: McGraw Hill; 2004. p. 826.
Beringer P. Remington: The Science and Practice of Pharmacy.
Philadelphia, PA: Lippincott Williams and Wilkins; 2011. p. 675.
Shekhawat PB, Pokharkar VB. Understanding peroral absorption:
Regulatory aspects and contemporary approaches to tackling solubility
and permeability hurdles. Acta Pharm Sin B 2017;7:260-80.
Manallack DT. The pK(a) distribution of drugs: Application to drug
discovery. Perspect Medicin Chem 2007;1:25-38.
Cheng F, Li W, Zhou Y, Shen J, Wu Z, Liu G, et al. AdmetSAR:
A comprehensive source and free tool for assessment of chemical
ADMET properties. J Chem Inf Model 2012;52:3099-105.
Daina A, Michielin O, Zoete V. SwissADME: A free web tool to
evaluate pharmacokinetics, drug-likeness and medicinal chemistry
friendliness of small molecules. Sci Rep 2017;7:42717.
QikProp Ver. 3.5. New York: Schrödinger LLC; 2012. p. 6.
Available from: http://www.gohom.win/ManualHom/Schrodinger/
Schrodinger_2012_docs/qikprop/qikprop_user_manual.pdf.
Swain M. Chemicalize.org. J Chem Inf Model 2012;52:613-5.
Pires DE, Blundell TL, Ascher DB. PkCSM: Predicting small-molecule
predicting small-molecule pharmacokinetic and toxicity properties
using graph-based signatures. J Med Chem 2015;58:4066-72.
Calculation of Molecular Properties and Bioactivity Score; 2018.
Available from: http://www.molinspiration.com/cgi-bin/properties.
[Last accessed on 2020 Mar 27].
Zhao YH, Abraham MH, Le J, Hersey A, Luscombe CN, Beck G, et al.
Rate-limited steps of human oral absorption and QSAR studies. Pharm
Res 2002;19:1446-57.
Lau ET, Giddings SJ, Mohammed SG, Dubois P, Johnson SK,
Stanley RA, et al. Encapsulation of hydrocortisone and mesalazine in
zein microparticles. Pharmaceutics 2013;5:277-93.
Takahashi K, Sakano H, Rytting JH, Numata N, Kuroda S, Mizuno N.
Influence of pH on the permeability of p-toluidine and aminopyrine
through shed snake skin as a model membrane. Drug Dev Ind Pharm
;27:159-64.
Fang B, Li P, Shi X, Chen F, Wang L. Incompatibilities of lornoxicam
with 4 antiemetic medications in polyole fi n bags during simulated
intravenous administration. Medicine (Baltimore) 2016;95:1-5.
Avdeef A, Berger CM. pH-metric solubility. 3. Dissolution titration
template method for solubility determination. Eur J Pharm Sci
;14:281-91.
Rodríguez-Barrientos D, Rojas-Hernández A, Gutiérrez A, Moya-
Hernández R, Gómez-Balderas R, Ramírez-Silva MT. Determination of
pKa values of tenoxicam from 1H NMR chemical shifts and of oxicams
from electrophoretic mobilities (CZE) with the aid of programs SQUAD
and HYPNMR. Talanta 2009;80:754-62.
Oliveira ÉD, Azevedo RD, Bonfilio R, De Oliveira DB,
Ribeiro GP, De Araújo MB. Dissolution test optimization for meloxicam
in the tablet pharmaceutical form. Braz J Pharm Sci 2009;45:67-73.
Juranic I, Dzeletovic D, Jovanovic J. Protolytic constants of nizatidine,
ranitidine and N, N ’-DIMETHYL-2-nitro-1, 1-ethenediamine.
Spectrophotometric and theoretical investigation. J Pharm Biomed
Anal 2015;15:1-18.
Ahmadi F, Karamian E. Computational aided-molecular imprinted
polymer design for solid phase extraction of metaproterenol from
plasma and determination by voltammetry using modified carbon
nanotube electrode. Iran J Pharm Res 2014;13:417-29.
Sheshala R. Validated high performance liquid chromatography
(HPLC) method for the determination of sumatriptan in rabbit plasma:
Application to pharmacokinetic study. Afr J Pharm Pharmacol
;6:98-107.
Nidhi K, Indrajeet S, Khushboo M, Gauri K, Sen DJ.
Hydrotropy: A promising tool for solubility enhancement: A review.
Int J Drug Dev Res 2011;3:26-33.
Gao H, Yao L, Mathieu HW, Zhang Y, Maurer TS, Troutman MD, et al.
In silico modeling of nonspecific binding to human liver microsomes.
Pharmacology 2008;36:2130-5.
Al-Deen AA, Dayo A, Ghoto MA, Arain MI, Parveen AQ. In vitro study
of stability, quality and quantity of some clinically and non-clinically
used cortisones from pharmaceutical preparations. Int J Biol Pharm
Allied Sci 2014;3:2720-33.
Du-Cuny L. Aqueous Solubility of Drug-like Compounds (Doctoral
Dissertation, Universitäts-und Landesbibliothek Bonn). Univ
Darmstadt; 2006.
Ahmad T. Modeling of ibuprofen II: Effect of pH on the adsorption
behavior on reversed phase liquid chromatography. Int J Appl Sci
Technol 2012;2:49-56.
Fillet M, Bechet I, Piette V, Crommen J. Separation of nonsteroidal
anti-inflammatory drugs by capillary electrophoresis using nonaqueous
electrolytes. Electrophoresis 1999;20:1907-15.
Comer JE, Manallack D. Ionization constants and ionization profiles.
Ref Modul Chem Mol Sci Chem Eng 2014; 8:357-97.
Raval G. Thermodynamic and Spectroscopic Studies on the Molecular
Interaction of Doxorubicin (DOX) with Negatively Charged Polymeric
Nanoparticles. University Toronto Master’s Theses; 2012. p. 65.
Margalit E, Kugler LJ, Brumm MV, Meza JL, Kompella UB,
Escobar ER, et al. The safety of intraocular ketorolac in rabbits.
Investig Ophthalmol Vis Sci 2006;47:2093-9.
Roche VF. The chemically elegant proton pump inhibitors. Am J Pharm
Educ 2006;70:101.
Yamashita F, Wanchana S, Hashida M. Quantitative structure/property
relationship analysis of Caco-2 permeability using a genetic algorithmbased
partial least squares method. Kyoto Univ 2002;91:2230-9.
Castillo-Garit JA, Marrero-Ponce Y, Torrens F. Estimation of ADME
properties in drug discovery: Predicting Caco-2 cell permeability using
atom-based stochastic and non-stochastic linear indices. Int Electron
Conf Synth Org Chem 2007;97:1-30.
Asuero AG, Sayago A, Gonz´alez AG. The correlation coefficient : An
overview. The correlation coefficient : An overview. J Crit Rev Anal
Chem 2006;36:41-59.
Settimo L, Bellman K, Knegtel RM. Comparison of the accuracy of
experimental and predicted pKa values of basic and acidic compounds.
Springer Sci 2013;31:86-8.
Lee AC, Crippen GM. Predicting pKa. Univ Michigan 2013;49:2013-33.
Frimayanti N, Yam ML, Lee HB, Othman R, Zain SM, Rahman NA.
Validation of quantitative structure activity relationship (QSAR) model
for photosensitizer activity prediction. Int J Mol Sci 2011;12:8626-44.
Alexander DL, Tropsha A, Winkler DA. Beware of R2: Simple,
unambiguous assessment of the prediction accuracy of QSAR and
QSPR models. J Chem Inf Model 2015;55:1316-22.