{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,21]],"date-time":"2026-06-21T04:49:09Z","timestamp":1782017349234,"version":"3.54.5"},"reference-count":59,"publisher":"SAGE Publications","license":[{"start":{"date-parts":[[2020,1,1]],"date-time":"2020-01-01T00:00:00Z","timestamp":1577836800000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2020,1,1]],"date-time":"2020-01-01T00:00:00Z","timestamp":1577836800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Bioinform Biol Insights"],"published-print":{"date-parts":[[2020,1]]},"abstract":"<jats:p>In this study, the interaction of selected pharmaceutical excipients on the function of P-glycoprotein (P-gp) and activity of 6 cytochrome P450 (CYP) isoforms were computationally investigated. At binding free energy cut-off value of \u22125.0\u2009kcal\/mol, the result showed possible modulatory or inhibitory effect by cethyl alcohol on CPY3A4 and P-gp; cetyltrimethyl-ammonium bromide (CTAB) on CYP1A2 and P-gp; dibutyl sebacate on CYP2C9, CYP2E1, and P-gp; sodium caprylate on CYP1A2 and CYP3A4; while most of the tested excipients have good interaction with the cytochromes and P-gp. The predicted pharmacokinetics provided possible inhibitors of the CYPs and P-gp and suggested that aspartame and acetyl tributyl citrate may not permeate blood\u2013brain barrier and not act as P-gp substrates. Target prediction for CTAB showed 100% and 35% probability of target to dynamin-1 (UniProt ID: Q05193) and histamine H3 receptor (UniProt ID: Q9Y5N1), respectively, whereas tricaprylin showed 40% probability of target to 5 Protein kinase C (UniProt IDs: P17252, Q02156, Q04759, P24723, and P05129). This study shows that synergistic effect of some excipients present in a drug formulation and multiple drugs administration is possible through modulation of CYPs activities and P-gp function, and this is crucial for consideration to mitigate toxicity in pediatric and adult populations.<\/jats:p>","DOI":"10.1177\/1177932220943183","type":"journal-article","created":{"date-parts":[[2020,7,27]],"date-time":"2020-07-27T12:54:01Z","timestamp":1595854441000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":9,"title":["In Silico Investigation of First-Pass Effect on Selected Small Molecule Excipients and Structural Dynamics of P-glycoprotein"],"prefix":"10.1177","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3202-9855","authenticated-orcid":false,"given":"Toluwase Hezekiah","family":"Fatoki","sequence":"first","affiliation":[{"name":"Translational Bioinformatics Unit, Department of Biochemistry, Federal University Oye-Ekiti, Oye-Ekiti, Nigeria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Omodele","family":"Ibraheem","sequence":"additional","affiliation":[{"name":"Translational Bioinformatics Unit, Department of Biochemistry, Federal University Oye-Ekiti, Oye-Ekiti, Nigeria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oladoja A","family":"Awofisayo","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical and Medicinal Chemistry, University of Uyo, Uyo, Nigeria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9528-5288","authenticated-orcid":false,"given":"Abiodun Samuel","family":"Oyedele","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Tennessee State University, Nashville, TN, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olapade Samuel","family":"Akinlolu","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Federal University Oye-Ekiti, Oye-Ekiti, Nigeria"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2020,7,27]]},"reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0169-409X(97)00039-2"},{"key":"e_1_3_2_3_2","first-page":"199","volume-title":"Pharmaceutical Excipients: Properties, Functionality, and Applications in Research and Industry","author":"Moreton RC","unstructured":"Moreton RC. Excipient standards and harmonization. In: Koo OMY, ed. Pharmaceutical Excipients: Properties, Functionality, and Applications in Research and Industry. 1st ed. Hoboken, NJ: John Wiley & Sons; 2017:199-240.","edition":"1"},{"key":"e_1_3_2_4_2","first-page":"269","volume-title":"Pharmaceutical Excipients: Properties, Functionality, and Applications in Research and Industry","author":"Kolter K","unstructured":"Kolter K, Guth F. Development of new excipients. In: Koo OMY, ed. Pharmaceutical Excipients: Properties, Functionality, and Applications in Research and Industry. 1st ed. Hoboken, NJ: John Wiley & Sons; 2017:269-301.","edition":"1"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1021\/acs.molpharmaceut.8b00482"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1021\/mp3001815."},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1021\/mp400175n."},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1517\/phgs.5.3.305.29827"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.2174\/1568026013395001"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0090-9556(24)15229-4"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.3390\/molecules23071820."},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms18112353."},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.addr.2015.03.001"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1359-6446(01)02100-6"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1067\/mcp.2000.109156."},{"key":"e_1_3_2_16_2","first-page":"1","volume-title":"Pharmaceutical Excipients: Properties, Functionality, and Applications in Research and Industry","author":"Good D","unstructured":"Good D, Wu Y. Excipient characterization. In: Koo OMY, ed. Pharmaceutical Excipients: Properties, Functionality, and Applications in Research and Industry, 1st ed. Hoboken, NJ: John Wiley & Sons; 2017:1-49.","edition":"1"},{"key":"e_1_3_2_17_2","first-page":"267","volume-title":"Excipient Toxicity and Safety","author":"Sullivan FM","unstructured":"Sullivan FM, Barlow SM. Toxicokinetics and hazard identification. In: Weiner ML, Kotkoskie LA, eds. Excipient Toxicity and Safety. New York, NY: Marcel Dekker, Inc.; 2000:267-281."},{"key":"e_1_3_2_18_2","first-page":"191","volume-title":"Topics on Drug Metabolism","author":"Jurica J","unstructured":"Jurica J, Sulcova A. Determination of cytochrome P450 metabolic activity using selective markers. In: Paxton J, ed. Topics on Drug Metabolism. Rijeka, Croatia: InTechOpen; 2012:191\u2013220."},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijpharm.2015.01.022."},{"key":"e_1_3_2_20_2","volume-title":"Handbook of Pharmaceutical Excipients","author":"Rowe RC","year":"2009","unstructured":"Rowe RC, Sheskey PJ, Quinn ME. Handbook of Pharmaceutical Excipients. 6th ed. London, England: Pharmaceutical Press; Washington, DC: American Pharmacists Association; 2009.","edition":"6"},{"key":"e_1_3_2_21_2","doi-asserted-by":"crossref","first-page":"1","DOI":"10.9734\/JAMPS\/2018\/45211","article-title":"Impacts of analogy and dimerization of bioactive compounds on molecular biological functions","volume":"19","author":"Fatoki TH","year":"2018","unstructured":"Fatoki TH, Awofisayo OA, Ogunyewo OA, Ugboko HU, Sanni DM. Impacts of analogy and dimerization of bioactive compounds on molecular biological functions. J Adv Medical Pharm Sci. 2018;19:1-14.","journal-title":"J Adv Medical Pharm Sci"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1002\/jcc.21256"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1002\/jcc.21334"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1038\/srep42717."},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gku293"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1177\/1177932219884297."},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pcbi.1005659"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1063\/1.1332996"},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.1063\/1.464397"},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gky356"},{"key":"e_1_3_2_31_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1359-6446(05)03580-4"},{"key":"e_1_3_2_32_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0093819."},{"key":"e_1_3_2_33_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.drudis.2011.1\/1.003."},{"key":"e_1_3_2_34_2","first-page":"3","article-title":"Interactions and incompatibilities of pharmaceutical excipients with active pharmaceutical ingredients: a comprehensive review","volume":"1","author":"Bharate SS","year":"2010","unstructured":"Bharate SS, Bharate SB, Bajaj AN. Interactions and incompatibilities of pharmaceutical excipients with active pharmaceutical ingredients: a comprehensive review. J Excipients Food Chem. 2010;1:3-26.","journal-title":"J Excipients Food Chem"},{"key":"e_1_3_2_35_2","doi-asserted-by":"publisher","DOI":"10.1021\/jm9701886"},{"key":"e_1_3_2_36_2","doi-asserted-by":"publisher","DOI":"10.1021\/jm9911027"},{"key":"e_1_3_2_37_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00919-06"},{"key":"e_1_3_2_38_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/28.1.235"},{"key":"e_1_3_2_39_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijpharm.2014.11.064."},{"key":"e_1_3_2_40_2","doi-asserted-by":"publisher","DOI":"10.1067\/mcp.2002.126409."},{"key":"e_1_3_2_41_2","doi-asserted-by":"publisher","DOI":"10.1093\/toxsci\/kfr178."},{"key":"e_1_3_2_42_2","first-page":"1","volume-title":"Final Amended Report on the Safety Assessment of Triglycerides as Used in Cosmetics","author":"Fiume MM","unstructured":"Fiume MM, ed. Final Amended Report on the Safety Assessment of Triglycerides as Used in Cosmetics. Washington, DC: Cosmetic Ingredient Review; 2018:1-40."},{"key":"e_1_3_2_43_2","doi-asserted-by":"publisher","DOI":"10.1191\/0960327106het646oa."},{"key":"e_1_3_2_44_2","doi-asserted-by":"publisher","DOI":"10.1177\/1091581814540480."},{"key":"e_1_3_2_45_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-08906-x."},{"key":"e_1_3_2_46_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M110.193151"},{"key":"e_1_3_2_47_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M109.047290"},{"key":"e_1_3_2_48_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0005-2736(98)00032-7"},{"key":"e_1_3_2_49_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M116.755884."},{"key":"e_1_3_2_50_2","doi-asserted-by":"publisher","DOI":"10.1021\/acs.biochem.5b00018"},{"key":"e_1_3_2_51_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0702807"},{"key":"e_1_3_2_52_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbamem.2014.07.018"},{"key":"e_1_3_2_53_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-827X(03)00079-X"},{"key":"e_1_3_2_54_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijpharm.2010.04.019"},{"key":"e_1_3_2_55_2","volume-title":"Consultation: Increased Online Access to Ingredient Information","author":"Therapeutic Goods Administration","year":"2019","unstructured":"Therapeutic Goods Administration. Consultation: Increased Online Access to Ingredient Information. Woden, ACT, Australia: Therapeutic Goods Administration; 2019. Reference\/Publication D19-5082856."},{"key":"e_1_3_2_56_2","doi-asserted-by":"publisher","DOI":"10.4414\/smw.2018.w14631."},{"key":"e_1_3_2_57_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejps.2014.09.004"},{"key":"e_1_3_2_58_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.maturitas.2017.11.001"},{"key":"e_1_3_2_59_2","doi-asserted-by":"publisher","DOI":"10.7363\/070112."},{"key":"e_1_3_2_60_2","first-page":"178","article-title":"The excipients between effects and the side effects","volume":"2","author":"Abdul-Bari MA.","year":"2019","unstructured":"Abdul-Bari MA. The excipients between effects and the side effects. J Med Care Res Rev. 2019;2:178-187.","journal-title":"J Med Care Res Rev"}],"container-title":["Bioinformatics and Biology Insights"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/1177932220943183","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.1177\/1177932220943183","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/1177932220943183","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T12:55:16Z","timestamp":1777380916000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1177\/1177932220943183"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,1]]},"references-count":59,"alternative-id":["10.1177\/1177932220943183"],"URL":"https:\/\/doi.org\/10.1177\/1177932220943183","relation":{},"ISSN":["1177-9322","1177-9322"],"issn-type":[{"value":"1177-9322","type":"print"},{"value":"1177-9322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,1]]},"article-number":"1177932220943183"}}