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Xenobiotica
the fate of foreign compounds in biological systems
Volume 48, 2018 - Issue 9
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Clinical Pharmacokinetics and Metabolism

Clinical evaluation of P-glycoprotein inhibition by venetoclax: a drug interaction study with digoxin

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Pages 904-910 | Received 30 Jul 2017, Accepted 15 Sep 2017, Published online: 13 Oct 2017

References

  • AbbVie, 2016. Venclexta® (venetoclax) [US prescribing information]. North Chicago (IL): AbbVie, Inc
  • Agarwal SK, DiNardo CD, Potluri J, et al. (2017a). Management of venetoclax-posaconazole interaction in acute myeloid leukemia patients: evaluation of dose adjustments. Clin Ther 39:359–67
  • Agarwal SK, Hu B, Chien D, et al. (2016). Evaluation of rifampin's transporter inhibitory and CYP3A inductive effects on the pharmacokinetics of venetoclax, a BCL-2 inhibitor: results of a single-a dn multiple-dose study. J Clin Pharmacol 56:1335–43
  • Agarwal SK, Salem AH, Danilov AV, et al. (2017b). Effect of ketoconazole, a strong CYP3A inhibitor, on the pharmacokinetics of venetoclax, a BCL-2 inhibitor, in patients with non-Hodgkin lymphoma. Br J Clin Pharmacol 83:846–54
  • Bauman JL, Didomenico RJ, Galanter WL. (2006). Mechanisms, manifestations and management of digoxin toxicity in the modern era. Am J Cardiovasc Drugs 6:77–86
  • Boehringer_Ingelheim, 2015. PRADAXA® (dabigatran etexilate mesylate) [US Prescribing Information]. Ridgefield (CT): Boehringer Ingelheim Pharmaceuticals, Inc
  • Bouchard L, Lévesque C, Pelletier N, et al. 2012. Improvement of sensitivity and robustness of an LCMSMS quantitation method for digoxin, controlling the reactivity of the deuterated internal standard. [online]. Available from: http://www.inventivhealthclinical.com/resource-library-posters.htm. [last accessed 18 Jul 2017]
  • Davids MS, Roberts AW, Seymour JF, et al. (2017). Phase I first-in-human study of venetoclax in patients with relapsed or refractory non-hodgkin lymphoma. J Clin Oncol 35:826–33
  • de Wit D, Schneider TC, Moes DJ, et al. (2016). Everolimus pharmacokinetics and its exposure-toxicity relationship in patients with thyroid cancer. Cancer Chemother Pharmacol 78:63–71
  • Delavenne X, Ollier E, Basset T, et al. (2013). A semi-mechanistic absorption model to evaluate drug-drug interaction with dabigatran: application with clarithromycin. Br J Clin Pharmacol 76:107–13
  • Finch A, Pillans P. (2014). P-glycoprotein and its role in drug-drug interactions. Australian Prescriber 37:137–9
  • Freise KJ, Dunbar M, Jones AK, et al. (2016a). Venetoclax does not prolong the QT interval in patients with hematological malignancies: an exposure-response analysis. Cancer Chemother Pharmacol 78:847–53
  • Freise KJ, Jones AK, Eckert D, et al. (2017a). Impact of venetoclax exposure on clinical efficacy and safety in patients with relapsed or refractory chronic lymphocytic leukemia. Clin Pharmacokinet 56:515–23
  • Freise KJ, Jones AK, Menon RM, et al. (2016b). Relationship between venetoclax exposure, rituximab coadministration, and progression-free survival in patients with relapsed or refractory chronic lymphocytic leukemia: demonstration of synergy. Hematol Oncol. [Epub ahead of print]. DOI: 10.1002/hon.2373
  • Freise KJ, Jones AK, Verdugo ME, et al. (2017b). Moving beyond maximum tolerated dose for targeted oncology drugs: use of clinical utility index to optimize venetoclax dosage in multiple myeloma patients. Clin Pharmacol Ther. [Epub ahead of print]. DOI: 10.1002/cpt.712
  • Freise KJ, Shebley M, Salem AH. (2017c). Quantitative prediction of the effect of CYP3A inhibitors and inducers on venetoclax pharmacokinetics using a physiologically based pharmacokinetic model. J Clin Pharmacol 57:796–804
  • Gurley BJ, Swain A, Williams DK, et al. (2008). Gauging the clinical significance of P-glycoprotein-mediated herb-drug interactions: comparative effects of St. John's wort, Echinacea, clarithromycin, and rifampin on digoxin pharmacokinetics. Mol Nutr Food Res 52:772–9
  • Jones AK, Freise KJ, Agarwal S, et al. (2016). Clinical predictors of venetoclax pharmacokinetics, a selective BCL-2 inhibitor, in chronic lymphocytic leukemia and Non-Hodgkin's lymphoma patients: a pooled population pharmacokinetic analysis. AAPS J 18:1192–202
  • Kikuchi R, Shebley M, Bow DA, et al. 2016. In vitro characterization of drug metabolizing enzymes and transporters to enable a mechanistic drug-drug interaction assessment for venetoclax. Poster session presented at: the International Society for the Study of Xenobiotics (ISSX); Busan, Korea, June 2016
  • Kishimoto W, Ishiguro N, Ludwig-Schwellinger E, et al. (2014). In vitro predictability of drug-drug interaction likelihood of P-glycoprotein-mediated efflux of dabigatran etexilate based on [I]2/IC50 threshold. Drug Metab Dispos 42:257–63
  • Konopleva M, Pollyea DA, Potluri J, et al. (2016). Efficacy and biological correlates of response in a phase II study of venetoclax monotherapy in patients with acute myelogenous leukemia. Cancer Discov 6:1106–17
  • Kullak-Ublick GA, Ismair MG, Stieger B, et al. (2001). Organic anion-transporting polypeptide B (OATP-B) and its functional comparison with three other OATPs of human liver. Gastroenterology 120:525–33
  • Lelievre LG, Philippe L. (2007). Mechanisms, manifestations, and management of digoxin toxicity. Heart and Metabolism 35:9–11
  • Liu H, Michmerhuizen M, Lao Y, et al. (2017). Metabolism and disposition of a novel B-cell lymphoma-2 inhibitor venetoclax in humans and characterization of its unusual metabolites. Drug Metab Dispos 45:294–305
  • Moreau P, Chanan-Khan A, Roberts AW, et al. (2017). Promising efficacy and acceptable safety of venetoclax plus bortezomib and dexamethasone in relapsed/ refractory MM. Blood. [Epub ahead of print]. doi: 10.1182/blood-2017-06-788323
  • Nader AM, Foster DR. (2014). Suitability of digoxin as a P-glycoprotein probe: implications of other transporters on sensitivity and specificity. J Clin Pharmacol 54:3–13
  • National Cancer Institute (2009). Common terminology criteria for adverse events (CTCAE), v4.0.3. Available from: http://ctep.cancer.gov/protocolDevelopment/electronic_applications/ctc.htm [last accessed 18 Jul 2017]
  • Oswald S, Terhaag B, Siegmund W. 2011. In Vivo probes of drug transport: commonly used probe drugs to assess function of intestinal p-glycoprotein (abcb1) in humans. In Fromm MF, Kim RB, eds. Drug transporters. Berlin, Heidelberg: Springer Berlin Heidelberg, 403–47
  • Parikh A, Gopalakrishnan S, Freise KJ, et al. (2017). Exposure-response evaluations of venetoclax efficacy and safety in patients with non-Hodgkin lymphoma. Leuk Lymphoma. [Epub ahead of print]. doi: 10.1080/10428194.2017.1361024
  • Pham PT, Pham PC, Danovitch GM, et al. (2004). Sirolimus-associated pulmonary toxicity. Transplantation 77:1215–20
  • Roberts AW, Davids MS, Pagel JM, et al. (2016). Targeting BCL2 with venetoclax in relapsed chronic lymphocytic leukemia. N Engl J Med 374:311–22
  • Robinson K, Johnston A, Walker S, et al. (1989). The digoxin-amiodarone interaction. Cardiovasc Drugs Ther 3:25–8
  • Salem AH, Agarwal SK, Dunbar M, et al. (2017a). Pharmacokinetics of venetoclax, a novel BCL-2 inhibitor, in patients with relapsed or refractory chronic lymphocytic leukemia or non-hodgkin lymphoma. J Clin Pharmacol 57:484–92
  • Salem AH, Agarwal SK, Dunbar M, et al. (2016). Effect of low- and high-fat meals on the pharmacokinetics of venetoclax, a selective first-in-class BCL-2 inhibitor. J Clin Pharmacol 56:1355–61
  • Salem AH, Dunbar M, Agarwal SK. (2017b). Pharmacokinetics of venetoclax in patients with 17p deletion chronic lymphocytic leukemia. Anticancer Drugs. 28:911–14
  • Salem AH, Hu B, Freise KJ, et al. (2017c). Evaluation of the pharmacokinetic interaction between venetoclax, a selective BCL-2 inhibitor, and warfarin in healthy volunteers. Clin Drug Investig 37:303–9
  • Seymour JF, Ma S, Brander DM, et al. (2017). Venetoclax plus rituximab in relapsed or refractory chronic lymphocytic leukaemia: a phase 1b study. Lancet Oncol 18:230–40
  • Shanafelt TD, Chaffee KG, Call TG, et al. (2015). Atrial fibrilation in patients with chronic lymphocytic leukemia (CLL). Blood 126:2950
  • Siepmann M, Kleinbloesem C, Kirch W. (1995). The interaction of the calcium antagonist RO 40-5967 with digoxin. Br J Clin Pharmacol 39:491–6
  • Stangier J, Stahle H, Rathgen K, et al. (2012). Pharmacokinetics and pharmacodynamics of dabigatran etexilate, an oral direct thrombin inhibitor, with coadministration of digoxin. J Clin Pharmacol 52:243–50
  • Taub ME, Mease K, Sane RS, et al. (2011). Digoxin is not a substrate for organic anion-transporting polypeptide transporters OATP1A2, OATP1B1, OATP1B3, and OATP2B1 but is a substrate for a sodium-dependent transporter expressed in HEK293 cells. Drug Metab Dispos 39:2093–102
  • United States food and Drug Administration (USFDA). (2012). Guidance for industry: drug interaction studies – study design, data analysis, implications for dosing, and labeling recommendations. Available from: http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM292362.pdf
  • Wessler JD, Grip LT, Mendell J, Giugliano RP. (2013). The P-glycoprotein transport system and cardiovascular drugs. J Am Coll Cardiol 61:2495–502
  • Zhang L. 2010. United States Food and Drug Administration: transporter-mediated drug-drug interactions (DDIs). Presented at the FDA Clinical Pharmacology Advisory Committee Meeting, Atlanta, GA, USA, March 2010

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