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Exploring the Relationship of Drug BCS Classification, Food Effect, and Gastric pH-Dependent Drug Interactions

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Abstract

Food effect (FE) and gastric pH-dependent drug-drug interactions (DDIs) are both absorption-related. Here, we evaluated if Biopharmaceutics Classification System (BCS) classes may be correlated with FE or pH-dependent DDIs. Trends in FE data were investigated for 170 drugs with clinical FE studies from the literature and new drugs approved from 2013 to 2019 by US Food and Drug Administration. A subset of 38 drugs was also evaluated to determine whether FE results can inform the need for a gastric pH-dependent DDI study. The results of FE studies were defined as no effect (AUC ratio 0.80–1.25), increased exposure (AUC ratio ≥1.25), or decreased exposure (AUC ratio ≤0.8). Drugs with significantly increased exposure FE (AUC ratio ≥2.0; N=14) were BCS Class 2 or 4, while drugs with significantly decreased exposure FE (AUC ratio ≤0.5; N=2) were BCS Class 1/3 or 3. The lack of FE was aligned with the lack of a pH-dependent DDI for all 7 BCS Class 1 or 3 drugs as expected. For the 13 BCS Class 2 or 4 weak base drugs with an increased exposure FE, 6 had a pH-dependent DDI (AUC ratio ≤0.8). Among the 16 BCS Class 2 or 4 weak base drugs with no FE, 6 had a pH-dependent DDI (AUC ratio ≤0.8). FE appears to have limited correlation with BCS classes except for BCS Class 1 drugs, confirming that multiple physiological mechanisms can impact FE. Lack of FE does not indicate absence of pH-dependent DDI for BCS Class 2 or 4 drugs.

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References

  1. US Food and Drug Administration. Guidance for Industry: assessing the effects of food on drugs in INDs and NDAs - Clinical Pharmacology Considerations (Draft Guidance). Silver Spring, MD: US Food and Drug Administration; 2019.

  2. US Food and Drug Administration. Guidance for Industry: bioequivalence studies with pharmacokinetic endpoints for drugs submitted under an ANDA (Draft Guidance). Silver Spring, MD: US Food and Drug Administration; 2013.

  3. O'Shea JP, Holm R, O'Driscoll CM, Griffin BT. Food for thought: formulating away the food effect - a PEARRL review. J Pharm Pharmacol. 2019;71(4):510–35.

    Article  CAS  PubMed  Google Scholar 

  4. Fleisher D, Li C, Zhou Y, Pao LH, Karim A. Drug, meal and formulation interactions influencing drug absorption after oral administration. Clinical implications. Clin Pharmacokinet. 1999;36(3):233–54.

    Article  CAS  PubMed  Google Scholar 

  5. Wu CY, Benet LZ. Predicting drug disposition via application of BCS: transport/absorption/ elimination interplay and development of a biopharmaceutics drug disposition classification system. Pharm Res. 2005;22(1):11–23.

    Article  CAS  PubMed  Google Scholar 

  6. Amidon GL, Lennernäs H, Shah VP, Crison JR. A theoretical basis for a biopharmaceutic drug classification: the correlation of in vitro drug product dissolution and in vivo bioavailability. Pharm Res. 1995;12(3):413–20.

    Article  CAS  PubMed  Google Scholar 

  7. US Food and Drug Administration. Guidance for Industry: waiver of in vivo bioavailability and bioequivalence studies for immediate-release solid oral dosage forms based on a biopharmaceutics classification system. US Food and Drug Administration: Silver Spring, MD; 2017.

    Google Scholar 

  8. Charman WN, Porter CJ, Mithani S, Dressman JB. Physiochemical and physiological mechanisms for the effects of food on drug absorption: the role of lipids and pH. J Pharm Sci. 1997;86(3):269–82.

    Article  CAS  PubMed  Google Scholar 

  9. Manallack DT. The pK(a) Distribution of drugs: application to drug discovery. Perspect Medicin Chem. 2007;1:25–38.

    Article  PubMed  PubMed Central  Google Scholar 

  10. Ji W. Pharmaceutical preformulation: the physicochemical properties of drug substances. Chichester (UK): Ellis Horwood; 1988.

    Google Scholar 

  11. Budha NR, Frymoyer A, Smelick GS, Jin JY, Yago MR, Dresser MJ, Holden SN, Benet LZ, Ware JA. Drug absorption interactions between oral targeted anticancer agents and PPIs: is pH-dependent solubility the Achilles heel of targeted therapy? Clin Pharmacol Ther. 2012;92(2):203–13.

    Article  CAS  PubMed  Google Scholar 

  12. Hamaguchi T, Shinkuma D, Irie T, Yamanaka Y, Morita Y, Iwamoto B, et al. Effect of a high-fat meal on the bioavailability of phenytoin in a commercial powder with a large particle size. Int J Clin Pharmacol Ther Toxicol. 1993;31(7):326–30.

    CAS  PubMed  Google Scholar 

  13. Custodio JM, Wu CY, Benet LZ. Predicting drug disposition, absorption/elimination/transporter interplay and the role of food on drug absorption. Adv Drug Deliv Rev. 2008;60(6):717–33.

    Article  CAS  PubMed  Google Scholar 

  14. Omachi F, Kaneko M, Iijima R, Watanabe M, Itagaki F. Relationship between the effects of food on the pharmacokinetics of oral antineoplastic drugs and their physicochemical properties. J Pharm Health Care Sci. 2019;5:26.

    Article  PubMed  PubMed Central  Google Scholar 

  15. Gu CH, Li H, Levons J, Lentz K, Gandhi RB, Raghavan K, Smith RL. Predicting effect of food on extent of drug absorption based on physicochemical properties. Pharm Res. 2007;24(6):1118–30.

    Article  CAS  PubMed  Google Scholar 

  16. International Consortium for Innovation & Quality in Pharmaceutical Development Comments to FDA Docket“Framework for Assessing pH-Dependent Drug-Drug Interactions”. 2018. https://iqconsortium.org/images/LG-DM/IQ_Comments_on_FDA_pH_DDIs_Docket_July2018.PDF.

  17. US Food and Drug Administration. Evaluation of Gastric pH-Dependent Drug Interactions With Acid-Reducing Agents: Study Design, Data Analysis, and Clinical Implications. 2020 Available from: https://www.fda.gov/regulatory-information/search-fda-guidance-documents/evaluation-gastric-ph-dependent-drug-interactions-acid-reducing-agents-study-design-data-analysis.

  18. Zhang L, Wu F, Lee SC, Zhao H. pH-dependent drug-drug interactions for weak base drugs: potential implications for new drug development. Clin Pharmacol Ther. 2014;96(2):266–77.

    Article  CAS  PubMed  Google Scholar 

  19. Strand DS, Kim D, Peura DA. 25 years of proton pump inhibitors: a comprehensive review. Gut Liver. 2017;11(1):27–37.

    Article  CAS  PubMed  Google Scholar 

  20. Gupta S, Banfield C, Affrime M, Marbury T, Padhi D, Glue P. Oral bioavailability of desloratadine is unaffected by food. Clin Pharmacokinet. 2002;41(Suppl 1):7–12.

    Article  CAS  PubMed  Google Scholar 

  21. Riedmaier AE, DeMent K, Huckle J, Bransford P, Stillhart C, Lloyd R, Alluri R, Basu S, Chen Y, Dhamankar V, Dodd S, Kulkarni P, Olivares-Morales A, Peng CC, Pepin X, Ren X, Tran T, Tistaert C, Heimbach T, et al. Use of physiologically based pharmacokinetic (PBPK) modeling for predicting drug-food interactions: an industry perspective. Aaps j. 2020;22(6):123.

    Article  CAS  PubMed  Google Scholar 

  22. Mithani SD, Bakatselou V, TenHoor CN, Dressman JB. Estimation of the increase in solubility of drugs as a function of bile salt concentration. Pharm Res. 1996;13(1):163–7.

    Article  CAS  PubMed  Google Scholar 

  23. Galia E, Nicolaides E, Hörter D, Löbenberg R, Reppas C, Dressman JB. Evaluation of various dissolution media for predicting in vivo performance of class I and II drugs. Pharm Res. 1998;15(5):698–705.

    Article  CAS  PubMed  Google Scholar 

  24. Hörter D, Dressman JB. Influence of physicochemical properties on dissolution of drugs in the gastrointestinal tract. Adv Drug Deliv Rev. 2001;46(1-3):75–87.

    Article  PubMed  Google Scholar 

  25. US Food and Drug Administration. Drug approval package: VASCEPA (icosapent) FDA application NDA 202057. Silver Spring, MD: US Food and Drug Administration; 2012.

  26. Lapointe JF, Harvey L, Aziz S, Jordan H, Hegele RA, Lemieux P. A single-dose, comparative bioavailability study of a formulation containing OM3 as phospholipid and free fatty acid to an ethyl ester formulation in the fasting and fed states. Clin Ther. 2019;41(3):426–44.

    Article  CAS  PubMed  Google Scholar 

  27. US Food and Drug Administration. Drug approval package: EPIDIOLEX (cannabidiol). FDA application NDA 210365. Silver Spring, MD: US Food and Drug Administration; 2015.

  28. US Food and Drug Administration. Drug approval package: ALECENSA (alectinib hydrochloride). FDA application NDA 208434. Silver Spring, MD: US Food and Drug Administration; 2015.

  29. Chi KN, Spratlin J, Kollmannsberger C, North S, Pankras C, Gonzalez M, Bernard A, Stieltjes H, Peng L, Jiao J, Acharya M, Kheoh T, Griffin TW, Yu MK, Chien C, Tran NP. Food effects on abiraterone pharmacokinetics in healthy subjects and patients with metastatic castration-resistant prostate cancer. J Clin Pharmacol. 2015;55(12):1406–14.

    Article  CAS  PubMed  Google Scholar 

  30. US Food and Drug Administration. Drug approval package: ZYTIGA (abiraterone acetate) FDA application NDA 202379. Silver Spring, MD: US Food and Drug Administration; 2011.

  31. US Food and Drug Administration. Drug approval package: OLUMIANT (baricitinib) FDA application NDA 207924. Silver Spring, MD: US Food and Drug Administration; 2018.

  32. Hens B, Tsume Y, Bermejo M, Paixao P, Koenigsknecht MJ, Baker JR, Hasler WL, Lionberger R, Fan J, Dickens J, Shedden K, Wen B, Wysocki J, Loebenberg R, Lee A, Frances A, Amidon G, Yu A, Benninghoff G, et al. Low Buffer Capacity and alternating motility along the human gastrointestinal tract: implications for in vivo dissolution and absorption of ionizable drugs. Mol Pharm. 2017;14(12):4281–94.

    Article  CAS  PubMed  Google Scholar 

  33. US Food and Drug Administration. Drug approval package: ODOMZO (sonidegib phosphate) FDA application NDA 205266. Silver Spring, MD: US Food and Drug Administration; 2015.

  34. US Food and Drug Administration. Drug approval package: TURALIO (pexidartinib hydrochloride) FDA application NDA 211810. Silver Spring, MD: US Food and Drug Administration; 2019.

  35. US Food and Drug Administration. Drug approval package: NERLYNX (neratinib maleate) FDA application NDA 208051. Silver Spring, MD: US Food and Drug Administration; 2017.

  36. Gong L, Fu C, Bi L, Kuang Y, Guo C, Wei G, Yan Z, Huang J, Yang G. Pharmacokinetics and bioequivalence of low-dose clopidogrel in healthy Chinese volunteers under fasted and fed conditions. Drug Metab Pharmacokinet. 2019;34(5):300–7.

    Article  CAS  PubMed  Google Scholar 

  37. Brvar N, Lachance S, Lévesque A, Breznik M, Cvitkovič Marčič L, Merslavič M, Grabnar I, Mateovič-Rojnik T. Comparative bioavailability of two oral formulations of clopidogrel: determination of clopidogrel and its carboxylic acid metabolite (SR26334) under fasting and fed conditions in healthy subjects. Acta Pharm. 2014;64(1):45–62.

    Article  CAS  PubMed  Google Scholar 

  38. US Food and Drug Administration. Drug approval package: PLAVIX (clopidogrel bisulfate). FDA application NDA 020839. Silver Spring, MD: US Food and Drug Administration; 2002.

  39. US Food and Drug Administration. Drug approval package: VENCLEXTA (venetoclax). FDA application NDA 208573. Silver Spring, MD: US Food and Drug Administration; 2016.

  40. Salem AH, Agarwal SK, Dunbar M, Enschede SL, Humerickhouse RA, Wong SL. Pharmacokinetics of venetoclax, a novel BCL-2 inhibitor, in patients with relapsed or refractory chronic lymphocytic leukemia or non-Hodgkin lymphoma. J Clin Pharmacol. 2017;57(4):484–92.

    Article  CAS  PubMed  Google Scholar 

  41. Salem AH, Agarwal SK, Dunbar M, Nuthalapati S, Chien D, Freise KJ, Wong SL. Effect of low- and high-fat meals on the pharmacokinetics of venetoclax, a selective first-in-classBCL-2 inhibitor. J Clin Pharmacol. 2016;56(11):1355–61.

    Article  CAS  PubMed  Google Scholar 

  42. Taylor L, Gidal B, Blakey G, Tayo B, Morrison G. A Phase I, Randomized, double-blind, placebo-controlled, single ascending dose, multiple dose, and food effect trial of the safety, tolerability and pharmacokinetics of highly purified cannabidiol in healthy subjects. CNS Drugs. 2018;32(11):1053–67.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Courtney R, Wexler D, Radwanski E, Lim J, Laughlin M. Effect of food on the relative bioavailability of two oral formulations of posaconazole in healthy adults. Br J Clin Pharmacol. 2004;57(2):218–22.

    Article  PubMed  PubMed Central  Google Scholar 

  44. Li H, Wei Y, Zhang S, Xu L, Jiang J, Qiu Y, Mangin E, Zhao XM, Xie S. Pharmacokinetics and safety of posaconazole administered by intravenous solution and oral tablet in healthy chinese subjects and effect of food on tablet bioavailability. Clin Drug Investig. 2019;39(11):1109–16.

    Article  PubMed  Google Scholar 

  45. US Food and Drug Administration. Drug approval package: NOXAFIL (posaconazole). FDA application NDA 022003. Silver Spring, MD: US Food and Drug Administration 2006.

  46. US Food and Drug Administration. Drug approval package: XERMELO (telotristat etiprate). FDA application NDA 208794. Silver Spring, MD: US Food and Drug Administration; 2017.

  47. Therapeutic Goods Administration. Australian Public Assessment Report for Alectinib hydrochloride. Canberra, ACT: Therapeutic Good Administration; 2017.

  48. Morcos PN, Guerini E, Parrott N, Dall G, Blotner S, Bogman K, Sturm C, Balas B, Martin-Facklam M, Phipps A. Effect of food and esomeprazole on the pharmacokinetics of alectinib, a highly selective alk inhibitor, in healthy subjects. Clin Pharmacol Drug Dev. 2017;6(4):388–97.

    Article  CAS  PubMed  Google Scholar 

  49. Oh DA, Parikh N, Khurana V, Cognata Smith C, Vetticaden S. Effect of food on the pharmacokinetics of dronabinol oral solution versus dronabinol capsules in healthy volunteers. Clin Pharmacol. 2017;9:9–17.

    CAS  PubMed  PubMed Central  Google Scholar 

  50. US Food and Drug Administration. Drug approval package: MARINOL (dronabinol). FDA application NDA 018651. Silver Spring, MD: US Food and Drug Administration; 1985.

  51. de Jong J, Sukbuntherng J, Skee D, Murphy J, O'Brien S, Byrd JC, et al. The effect of food on the pharmacokinetics of oral ibrutinib in healthy participants and patients with chronic lymphocytic leukemia. Cancer Chemother Pharmacol. 2015;75(5):907–16.

    Article  PubMed  PubMed Central  Google Scholar 

  52. US Food and Drug Administration. Drug approval package: IMBRUVICA (ibrutinib). FDA application NDA 205552. Silver Spring, MD: US Food and Drug Administration; 2013.

  53. US Food and Drug Administration. Drug approval package: OSPHENA (ospemifene). FDA application NDA 203505. Silver Spring, MD: US Food and Drug Administration 2013.

  54. Preskorn S, Ereshefsky L, Chiu YY, Poola N, Loebel A. Effect of food on the pharmacokinetics of lurasidone: results of two randomized, open-label, crossover studies. Hum Psychopharmacol. 2013;28(5):495–505.

    Article  CAS  PubMed  Google Scholar 

  55. US Food and Drug Administration. Drug approval package: LATUDA (lurasidone hydrochloride). FDA application NDA 200603. Silver Spring, MD: US Food and Drug Administration 2010.

  56. Li X, Zhang H, Zhu X, Li C, Chen H, Liu J, Chen G, Wu M, Liu C, Shen Z, Niu J, Liu B, Ding Y. Pharmacokinetics and safety profile of desmopressin oral tablet formulations in healthy Chinese subjects under fasting and fed conditions. Int J Clin Pharmacol Ther. 2018;56(9):434–42.

    Article  CAS  PubMed  Google Scholar 

  57. US Food and Drug Administration. Drug Approval Package: DDVAP (desmopressin acetate). FDA application NDA 019955. Silver Spring, MD: US Food and Drug Administration 1995.

  58. US Food and Drug Administration. Drug approval package: VIBERZI (eluxadoline). FDA application NDA 206940. Silver Spring, MD: US Food and Drug Administration 2015.

  59. US Food and Drug Administration. Drug approval package: CERDELGA (eliglustat tartrate). FDA application NDA 205494. Silver Spring, MD: US Food and Drug Administration 2014.

  60. US Food and Drug Administration. Drug approval package: COTELLIC (cobimetinib fumarate). FDA application NDA 206192. US Food and Drug Administration 2015.

  61. US Food and Drug Administration. Drug approval package: CRESEMBA (isavuconazonium sulfate). FDA application NDA 207500. Silver Spring, MD: US Food and Drug Administration; 2015.

  62. Schmitt-Hoffmann A, Desai A, Kowalski D, Pearlman H, Yamazaki T, Townsend R. Isavuconazole absorption following oral administration in healthy subjects is comparable to intravenous dosing, and is not affected by food, or drugs that alter stomach pH. Int J Clin Pharmacol Ther. 2016;54(8):572–80.

    Article  CAS  PubMed  Google Scholar 

  63. de Jong J, Haddish-Berhane N, Hellemans P, Jiao J, Sukbuntherng J, Ouellet D. The pH-altering agent omeprazole affects rate but not the extent of ibrutinib exposure. Cancer Chemother Pharmacol. 2018;82(2):299–308.

    Article  PubMed  Google Scholar 

  64. Sharma MR, Karrison TG, Kell B, Wu K, Turcich M, Geary D, Kang SP, Takebe N, Graham RA, Maitland ML, Schilsky RL, Ratain MJ, Cohen EEW. Evaluation of food effect on pharmacokinetics of vismodegib in advanced solid tumor patients. Clin Cancer Res. 2013;19(11):3059–67.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Malhi V, Colburn D, Williams SJ, Hop CE, Dresser MJ, Chandra P, et al. A clinical drug-drug interaction study to evaluate the effect of a proton-pump inhibitor, a combined P-glycoprotein/cytochrome 450 enzyme (CYP)3A4 inhibitor, and a CYP2C9 inhibitor on the pharmacokinetics of vismodegib. Cancer Chemother Pharmacol. 2016;78(1):41–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. US Food and Drug Administration. Drug approval package: TIVICAY (dolutegravir sodium). FDA application NDA 204790. Silver Spring, MD: US Food and Drug Administration; 2013.

  67. Nguyen L, Holland J, Mamelok R, Laberge MK, Grenier J, Swearingen D, Armas D, Lacy S. Evaluation of the effect of food and gastric pH on the single-dose pharmacokinetics of cabozantinib in healthy adult subjects. J Clin Pharmacol. 2015;55(11):1293–302.

    Article  CAS  PubMed  Google Scholar 

  68. Yokota H, Sato K, Okuda Y, Kobayashi H, Takeda M, Asano M, Ito H, Miura M. Effects of histamine 2-receptor antagonists and proton pump inhibitors on the pharmacokinetics of gefitinib in patients with non-small-cell lung cancer. Clin Lung Cancer. 2017;18(6):e433–e9.

    Article  CAS  PubMed  Google Scholar 

  69. Zhang H, Li Q, Zhu X, Wu M, Li C, Li X, Liu C, Shen Z, Ding Y, Hua S. Association of variability and pharmacogenomics with bioequivalence of gefitinib in healthy male subjects. Front Pharmacol. 2018;9:849.

    Article  PubMed  PubMed Central  Google Scholar 

  70. European Medicines Agency. Assessment report: zontivity (vorapaxar). London, UK: European Medicines Agency; 2014.

  71. Kosoglou T, Reyderman L, Tseng J, Kumar B, Xuan F, Schiller J, Meehan AG, Kim K, Cutler DL. Effect of food, antacid, and age on the pharmacokinetics of the oral thrombin receptor antagonist vorapaxar (SCH 530348) in healthy volunteers. Clin Pharmacol Drug Dev. 2013;2(3):223–30.

    Article  CAS  PubMed  Google Scholar 

  72. Behm MO, Kosoglou T, Miltenburg AM, Li J, Statkevich P, Johnson-Levonas AO, et al. The Absence of a Clinically Significant Effect of Food on the Single Dose Pharmacokinetics of Vorapaxar, a PAR-1 Antagonist, in Healthy Adult Subjects. Clin Pharmacol Drug Dev. 2013;2(4):310–5.

    Article  CAS  PubMed  Google Scholar 

  73. US Food and Drug Administration. Drug Approval Package: ZONTIVITY (vorapaxar sulfate). FDA application NDA 204886. Silver Spring, MD: US Food and Drug Administration; 2014.

  74. US Food and Drug Administration. Drug Approval Package: OXBRYTA (voxelotor). FDA application NDA 213137. Silver Spring, MD: US Food and Drug Administration; 2019.

  75. Zhang M, Xu C, Ma L, Shamiyeh E, Yin J, von Moltke LL, Smith WB. Effect of food on the bioavailability and tolerability of the JAK2-selective inhibitor fedratinib (SAR302503): results from two phase I studies in healthy volunteers. Clin Pharmacol Drug Dev. 2015;4(4):315–21.

    Article  CAS  PubMed  Google Scholar 

  76. US Food and Drug Administration. Drug approval package: INREBIC (fedratinib hydrochloride). FDA application NDA 212327. Silver Spring, MD: US Food and Drug Administration; 2019.

  77. Sun W, Klamerus KJ, Yuhas LM, Pawlak S, Plotka A, O'Gorman M, Kirkovsky L, Kosa M, Wang D. Impact of acid-reducing agents on the pharmacokinetics of palbociclib, a weak base with pH-dependent solubility, with different food intake conditions. Clin Pharmacol Drug Dev. 2017;6(6):614–26.

    Article  CAS  PubMed  Google Scholar 

  78. US Food and Drug Administration. Drug approval package: IBRANCE (palbociclib). FDA application NDA 207103. Silver Spring, MD: US Food and Drug Administration 2015.

  79. Behm MO, Yee KL, Liu R, Levine V, Panebianco D, Fackler P. The effect of food on doravirine bioavailability: results from two pharmacokinetic studies in healthy subjects. Clin Drug Investig. 2017;37(6):571–9.

    Article  CAS  PubMed  Google Scholar 

  80. US Food and Drug Administration. Drug approval package: PIFELTRO (doravirine). FDA application NDA 210806. Silver Spring, MD: US Food and Drug Administration 2018.

  81. US Food and Drug Administration. Drug approval package: ROZLYTREK (entrectinib). FDA application NDA 212725. Silver Spring, MD: US Food and Drug Administration 2019.

  82. Ruiz-Garcia A, Masters JC. Mendes da Costa L, LaBadie RR, Liang Y, Ni G, et al. Effect of food or proton pump inhibitor treatment on the bioavailability of dacomitinib in healthy volunteers. J Clin Pharmacol. 2016;56(2):223–30.

    Article  CAS  PubMed  Google Scholar 

  83. US Food and Drug Administration. Drug approval package: OCALIVA (obeticholic acid). FDA application NDA 207999. Silver Spring, MD: US Food and Drug Administration 2016.

  84. US Food and Drug Administration. Drug approval package: BRAFTOVI (encorafenib). FDA application NDA 210496. Silver Spring, MD: US Food and Drug Administration 2018.

  85. US Food and Drug Administration. Drug approval package: REXULTI (brexpiprazole). FDA application NDA 205422. Silver Spring, MD: US Food and Drug Administration 2015.

  86. European Medicines Agency. Assessment report: calquence (acalabrutinib). London, UK: European Medicines Agency; 20120.

  87. US Food and Drug Administration. Drug approval package: CALQUENCE (acalabrutinib). FDA application NDA 210259. Silver Spring, MD: US Food and Drug Administration 2017.

  88. US Food and Drug Administration. Drug approval package: ADEMPAS (riociguat). FDA application NDA 204819. Silver Spring, MD: US Food and Drug Administration 2013.

  89. US Food and Drug Administration. Drug approval package: DAKLINZA (daclatasvir dihydrochloride). FDA application NDA 206843. Silver Spring, MD: US Food and Drug Administration 2015.

  90. US Food and Drug Administration. Drug approval package: TAFINLAR (dabrafenib mesylate). FDA application NDA 202806. Silver Spring, MD: US Food and Drug Administration 2013.

  91. Vishwanathan K, Dickinson PA, Bui K, Cassier PA, Greystoke A, Lisbon E, Moreno V, So K, Thomas K, Weilert D, Yap TA, Plummer R. The effect of food or omeprazole on the pharmacokinetics of osimertinib in patients with non-small-cell lung cancer and in healthy volunteers. J Clin Pharmacol. 2018;58(4):474–84.

    Article  CAS  PubMed  Google Scholar 

  92. US Food and Drug Administration. Drug approval package: TAGRISSO (osimertinib mesylate). FDA application NDA 208065. Silver Spring, MD: US Food and Drug Administration 2015.

  93. Laille E, Savona MR, Scott BL, Boyd TE, Dong Q, Skikne B. Pharmacokinetics of different formulations of oral azacitidine (CC-486) and the effect of food and modified gastric pH on pharmacokinetics in subjects with hematologic malignancies. J Clin Pharmacol. 2014;54(6):630–9.

    Article  CAS  PubMed  Google Scholar 

  94. US Food and Drug Administration. Drug approval package: BEVYXXA (betrixaban). FDA application NDA 208383. Silver Spring, MD: US Food and Drug Administration 2017.

  95. Keyvanjah K, DiPrimeo D, Li A, Obaidi M, Swearingen D, Wong A. Pharmacokinetics of neratinib during coadministration with lansoprazole in healthy subjects. Br J Clin Pharmacol. 2017;83(3):554–61.

    Article  CAS  PubMed  Google Scholar 

  96. Lau YY, Gu W, Lin T, Song D, Yu R, Scott JW. Effects of meal type on the oral bioavailability of the ALK inhibitor ceritinib in healthy adult subjects. J Clin Pharmacol. 2016;56(5):559–66.

    Article  CAS  PubMed  Google Scholar 

  97. US Food and Drug Administration. Drug approval package: ZYKADIA (ceritinib). FDA application NDA 205755. Silver Spring, MD: US Food and Drug Administration 2014.

  98. US Food and Drug Administration. Drug approval package: LORBRENA (lorlatinib). FDA application NDA 210868. Silver Spring, MD: US Food and Drug Administration 2018.

  99. US Food and Drug Administration D. Drug approval package: SAVAYSA (edoxaban tosylate). FDA application NDA 206316. Silver Spring, MD: US Food and Drug Administration 2015.

  100. US Food and Drug Administration. Drug approval package: UBRELVY (ubrogepant). FDA application NDA 211765. Silver Spring, MD: US Food and Drug Administration 2019.

  101. US Food and Drug Administration. Drug approval package: MEKTOVI (binimetinib). FDA application NDA 210498. Silver Spring, MD: US Food and Drug Administration 2018.

  102. Munchhof MJ, Li Q, Shavnya A, Borzillo GV, Boyden TL, Jones CS, LaGreca SD, Martinez-Alsina L, Patel N, Pelletier K, Reiter LA, Robbins MD, Tkalcevic GT. Discovery of PF-04449913, a Potent and Orally Bioavailable Inhibitor of Smoothened. ACS Med Chem Lett. 2012;3(2):106–11.

    Article  CAS  PubMed  Google Scholar 

  103. Shaik MN, LaBadie RR, Rudin D, Levin WJ. Evaluation of the effect of food and ketoconazole on the pharmacokinetics of the smoothened inhibitor PF-04449913 in healthy volunteers. Cancer Chemother Pharmacol. 2014;74(2):411–8.

    Article  CAS  PubMed  Google Scholar 

  104. Giri N, Lam LH, LaBadie RR, Krzyzaniak JF, Jiang H, Hee B, et al. Evaluation of the effect of new formulation, food, or a proton pump inhibitor on the relative bioavailability of the smoothened inhibitor glasdegib (PF-04449913) in healthy volunteers. Cancer Chemother Pharmacol. 2017;80(6):1249–60.

    Article  CAS  PubMed  Google Scholar 

  105. Shaik N, Hee B, Wei H, LaBadie RR. Evaluation of the effects of formulation, food, or a proton-pump inhibitor on the pharmacokinetics of glasdegib (PF-04449913) in healthy volunteers: a randomized phase I study. Cancer Chemother Pharmacol. 2019;83(3):463–72.

    Article  CAS  PubMed  Google Scholar 

  106. US Food and Drug Administration. Drug approval package: DAURISMO (glasdegib maleate). FDA application NDA 210656. Silver Spring, MD: US Food and Drug Administration 2018.

  107. Mogalian E, German P, Kearney BP, Yang CY, Brainard D, Link J, et al. Preclinical pharmacokinetics and first-in-human pharmacokinetics, safety, and tolerability of velpatasvir, a pangenotypic hepatitis C virus NS5A inhibitor, in healthy subjects. Antimicrob Agents Chemother. 2017;61(5):e02084–16.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  108. US Food and Drug Administration. Drug approval package: EPCLUSA (sofosbuvir; velpatasvir). FDA application NDA 208341. Silver Spring, MD: US Food and Drug Administration 2016.

  109. Zhou J, Quinlan M, Glenn K, Boss H, Picard F, Castro H, Sellami D. Effect of esomeprazole, a proton pump inhibitor on the pharmacokinetics of sonidegib in healthy volunteers. Br J Clin Pharmacol. 2016;82(4):1022–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  110. European Medicines Agency. Assessment report: Iclusig (ponatinib). London, UK: European Medicines Agency; 2013.

    Google Scholar 

  111. Narasimhan NI, Dorer DJ, Niland K, Haluska F, Sonnichsen D. Effects of food on the pharmacokinetics of ponatinib in healthy subjects. J Clin Pharm Ther. 2013;38(6):440–4.

    Article  CAS  PubMed  Google Scholar 

  112. Narasimhan NI, Dorer DJ, Davis J, Turner CD, Sonnichsen D. Evaluation of the effect of multiple doses of lansoprazole on the pharmacokinetics and safety of ponatinib in healthy subjects. Clin Drug Investig. 2014;34(10):723–9.

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Pharmaceutics, University of Washington, H-272 Health Sciences Building, Box 357610, Seattle, Washington, 98195, USA

    Katie Owens, Sophie Argon, Jingjing Yu & Isabelle Ragueneau-Majlessi

  2. Office of Clinical Pharmacology, Office of Translational Sciences, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland, USA

    Xinning Yang & Anuradha Ramamoorthy

  3. Office of Research and Standards, Office of Generic Drugs, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland, USA

    Fang Wu, Sue-Chih Lee, Wei-Jhe Sun & Lei Zhang

Authors
  1. Katie Owens
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  2. Sophie Argon
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  10. Isabelle Ragueneau-Majlessi
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Contributions

Substantial contributions to the conception or design of the work or the acquisition, analysis, or interpretation of data for the work (KO, SA, JY, IR, XY, FW, SL, WS, AR, LZ)

Drafting the work or revising it critically for important intellectual content (KO, SA, JY, IR, XY, FW, SL, AR, LZ)

Final approval of the version to be published (KO, SA, JY, IR, XY, FW, SL, AR, LZ)

Agreement to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved (KO, SA, JY, IR, XY, FW, SL, AR, LZ)

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Correspondence to Katie Owens.

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The views expressed in this article are those of the authors and should not be construed to represent the US Food and Drug Administration’s views or policies. The mention of commercial products, their sources, or their use in connection with material reported herein is not to be construed as either an actual or implied endorsement of such products by the US Food and Drug Administration. This article reflects the views of the authors and should not be construed to represent FDA’s views or policies.

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Owens, K., Argon, S., Yu, J. et al. Exploring the Relationship of Drug BCS Classification, Food Effect, and Gastric pH-Dependent Drug Interactions. AAPS J 24, 16 (2022). https://doi.org/10.1208/s12248-021-00667-w

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