{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T03:13:54Z","timestamp":1789442034811,"version":"build-2803163510"},"reference-count":29,"publisher":"American Society for Microbiology","issue":"6","license":[{"start":{"date-parts":[[2012,6,1]],"date-time":"2012-06-01T00:00:00Z","timestamp":1338508800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2012,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>Eltrombopag is an orally bioavailable thrombopoietin receptor agonist that is approved for the treatment of chronic idiopathic thrombocytopenic purpura. It is being developed for other medical disorders that are associated with thrombocytopenia. Patients with human immunodeficiency virus (HIV) may suffer from thrombocytopenia as a result of their HIV disease or coinfection with hepatitis C virus (HCV). HIV medications, particularly ritonavir (RTV)-boosted HIV protease inhibitors, are involved in many drug interactions. This study evaluated the potential drug-drug interaction between eltrombopag and lopinavir (LPV)\/RTV. Forty healthy adult subjects enrolled in this open-label, three-period, single-sequence crossover study received a single 100-mg dose of eltrombopag (period 1), LPV\/RTV at 400\/100 mg twice daily (BID) for 14 days (period 2), and LPV\/RTV at 400\/100 mg BID (2 doses) with a single 100-mg dose of eltrombopag administered with the morning LPV\/RTV dose (period 3). There was a 3-day washout between periods 1 and 2 and no washout between periods 2 and 3. Serial pharmacokinetic samples were collected during 72 h in periods 1 and 3 and during 12 h in period 2. The coadministration of 400\/100 mg LPV\/RTV BID with a single dose of 100 mg eltrombopag decreased the plasma eltrombopag area under the plasma concentration-time curve from time zero extrapolated to infinity (AUC<jats:sub>0-\u221e<\/jats:sub>) by 17%, on average, with no change in plasma LPV\/RTV exposure. Adverse events (AEs) reported in period 2 were consistent with known LPV\/RTV AEs, such as diarrhea, abdominal pain, nausea, vomiting, rash, and fatigue. No subjects withdrew due to AEs, and no serious AEs were reported. These study results suggest that platelet counts should be monitored and the eltrombopag dose adjusted accordingly if LPV\/RTV therapy is initiated or discontinued.<\/jats:p>","DOI":"10.1128\/aac.05214-11","type":"journal-article","created":{"date-parts":[[2012,3,6]],"date-time":"2012-03-06T05:49:51Z","timestamp":1331012991000},"page":"2846-2851","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":17,"title":["Assessment of the Pharmacokinetic Interaction between Eltrombopag and Lopinavir-Ritonavir in Healthy Adult Subjects"],"prefix":"10.1128","volume":"56","author":[{"given":"Mary B.","family":"Wire","sequence":"first","affiliation":[{"name":"Clinical Pharmacology, GlaxoSmithKline, Research Triangle Park, North Carolina, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heidi B.","family":"McLean","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology, GlaxoSmithKline, Research Triangle Park, North Carolina, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carolyn","family":"Pendry","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology, GlaxoSmithKline, Research Triangle Park, North Carolina, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dickens","family":"Theodore","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology, GlaxoSmithKline, Research Triangle Park, North Carolina, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jung W.","family":"Park","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology, GlaxoSmithKline, Research Triangle Park, North Carolina, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bin","family":"Peng","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology, GlaxoSmithKline, Research Triangle Park, North Carolina, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","unstructured":"Abbott Laboratories. 2011. Kaletra (lopinavir\/ritonavir) tablets and oral solution product monograph. Abbott Laboratories North Chicago IL."},{"key":"e_1_3_2_3_2","volume-title":"Abstr. 62nd Am. Assoc. Study Liver Dis. Annu. Meet. American Association for the Study of Liver Diseases","author":"Afdhal N","year":"2011","unstructured":"AfdhalN. 2011. Final results of ENABLE 1, a phase 3, multicenter study of eltrombopag as an adjunct for antiviral treatment of hepatitis C Virus-related chronic liver disease associated with thrombocytopenia, abstract LB-3. Abstr. 62nd Am. Assoc. Study Liver Dis. Annu. Meet. American Association for the Study of Liver Diseases, Alexandria, VA."},{"key":"e_1_3_2_4_2","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1111\/j.1365-2125.2011.03972.x","article-title":"Eltrombopag increases plasma rosuvastatin exposure in healthy volunteers","volume":"72","author":"Allred AJ","year":"2011","unstructured":"AllredAJ. 2011. Eltrombopag increases plasma rosuvastatin exposure in healthy volunteers. Br. J. Clin. Pharmacol. 72:321\u2013329.","journal-title":"Br. J. Clin. Pharmacol."},{"key":"e_1_3_2_5_2","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1097\/QAI.0b013e3181be73e3","article-title":"Incidence and risk factors of thrombocytopenia in patients receiving intermittent antiretroviral therapy: a substudy of the ANRS 106-window trial","volume":"52","author":"Bouldouyre M-A","year":"2009","unstructured":"BouldouyreM-A. 2009. Incidence and risk factors of thrombocytopenia in patients receiving intermittent antiretroviral therapy: a substudy of the ANRS 106-window trial. J. Acquir. Immune Defic. Syndr 52:531\u2013537.","journal-title":"J. Acquir. Immune Defic. Syndr"},{"key":"e_1_3_2_6_2","volume-title":"12th Int. Workshop Clin. Pharmacol. HIV Ther","author":"Burger D","year":"2011","unstructured":"BurgerD JacobsBS ColbersEPH Velthoven-GraaflandK SchouwenbergBJJW. 2011. Effect of fosamprenavir\/ritonavir on the pharmacokinetics of single-dose olanzapine in healthy volunteers, abstr P-10. 12th Int. Workshop Clin. Pharmacol. HIV Ther."},{"key":"e_1_3_2_7_2","doi-asserted-by":"crossref","first-page":"2237","DOI":"10.1056\/NEJMoa073275","article-title":"Eltrombopag for the treatment of chronic idiopathic thrombocytopenic purpura","volume":"357","author":"Bussel JB","year":"2007","unstructured":"BusselJB. 2007. Eltrombopag for the treatment of chronic idiopathic thrombocytopenic purpura. N. Engl. J. Med. 357:2237\u20132247.","journal-title":"N. Engl. J. Med."},{"key":"e_1_3_2_8_2","doi-asserted-by":"crossref","first-page":"641","DOI":"10.1016\/S0140-6736(09)60402-5","article-title":"Effect of eltrombopag on platelet counts and bleeding during treatment of chronic idiopathic thrombocytopenic purpura: a randomized, double-blind, placebo-controlled trial","volume":"373","author":"Bussel JB","year":"2009","unstructured":"BusselJB. 2009. Effect of eltrombopag on platelet counts and bleeding during treatment of chronic idiopathic thrombocytopenic purpura: a randomized, double-blind, placebo-controlled trial. Lancet 373:641\u2013648.","journal-title":"Lancet"},{"key":"e_1_3_2_9_2","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1016\/S0140-6736(10)60959-2","article-title":"Eltrombopag for management of chronic immune thrombocytopenia (RAISE): a 6-month, randomized, phase 3 study","volume":"377","author":"Cheng G","year":"2011","unstructured":"ChengG. 2011. Eltrombopag for management of chronic immune thrombocytopenia (RAISE): a 6-month, randomized, phase 3 study. 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A phenotype-genotype approach to predicting CYP450 and P-glycoprotein drug interactions with the mixed inhibitor\/inducer tipranavir\/ritonavir. Clin. Pharmacol. Ther. 87:735\u2013742.","journal-title":"Clin. Pharmacol. Ther."},{"key":"e_1_3_2_12_2","doi-asserted-by":"crossref","first-page":"424","DOI":"10.1634\/stemcells.2008-0366","article-title":"Preclinical activity of eltrombopag (SB-497115), an oral, non-peptide thrombopoietin receptor agonist","volume":"27","author":"Erickson-Miller CL","year":"2009","unstructured":"Erickson-MillerCL. 2009. Preclinical activity of eltrombopag (SB-497115), an oral, non-peptide thrombopoietin receptor agonist. Stem Cells 27:424\u2013430.","journal-title":"Stem Cells"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1345\/aph.1K615"},{"key":"e_1_3_2_14_2","unstructured":"GlaxoSmithKline. 2011. Promacta (eltrombopag) tablets product monograph. 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A randomized, double-blind, placebo-controlled dose ranging study to assess the efficacy and safety of eltrombopag in patients receiving carboplatin\/paclitaxel for advanced solid tumors. Curr. Med. Res. Opin. 26:2339\u20132346.","journal-title":"Curr. Med. Res. Opin."},{"key":"e_1_3_2_19_2","doi-asserted-by":"crossref","first-page":"2329","DOI":"10.1124\/dmd.111.038646","article-title":"Complex drug interactions of hiv protease inhibitors 2: in vivo induction and in vitro correlation of induction of cytochrome P450 1A2, 2B6, and 2C9 by ritonavir or nelfinavir","volume":"39","author":"Kirby BJ","year":"2011","unstructured":"KirbyBJ. 2011. Complex drug interactions of hiv protease inhibitors 2: in vivo induction and in vitro correlation of induction of cytochrome P450 1A2, 2B6, and 2C9 by ritonavir or nelfinavir. Drug Metab. Dispos. 39:2329\u20132337.","journal-title":"Drug Metab. 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Risk factors for thrombocytopenia in HIV-infected persons in the era of potent antiretroviral therapy. J. Acquir. Immune Defic. Syndr. 52:595\u2013599.","journal-title":"J. Acquir. Immune Defic. Syndr."},{"key":"e_1_3_2_24_2","doi-asserted-by":"crossref","first-page":"2227","DOI":"10.1056\/NEJMoa073255","article-title":"Eltrombopag for thrombocytopenia in patients with cirrhosis associated with hepatitis C","volume":"357","author":"McHutchison JG","year":"2007","unstructured":"McHutchisonJG. 2007. Eltrombopag for thrombocytopenia in patients with cirrhosis associated with hepatitis C. N. Engl. J. Med. 357:2227\u20132236.","journal-title":"N. Engl. J. Med."},{"key":"e_1_3_2_25_2","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1159\/000313782","article-title":"An overview of the mechanisms of HIV-related thrombocytopenia","volume":"124","author":"Passos AM","year":"2010","unstructured":"PassosAM TreitingerA SpadaC. 2010. An overview of the mechanisms of HIV-related thrombocytopenia. Acta Haematol. 124:13\u201318.","journal-title":"Acta Haematol."},{"key":"e_1_3_2_26_2","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1016\/j.clpt.2006.04.014","article-title":"Lopinavir\/ritonavir reduces lamotrigine plasma concentrations in healthy subjects","volume":"80","author":"Van der Lee MJ","year":"2006","unstructured":"Van der LeeMJ. 2006. Lopinavir\/ritonavir reduces lamotrigine plasma concentrations in healthy subjects. Clin. Pharmacol. Ther. 80:159\u2013168.","journal-title":"Clin. Pharmacol. Ther."},{"key":"e_1_3_2_27_2","doi-asserted-by":"crossref","first-page":"825","DOI":"10.1177\/135965350701200510","article-title":"Abacavir plasma pharmacokinetics in the absence and presence of atazanavir\/ritonavir or lopinavir\/ritonavir and vice versa in HIV-infected patients","volume":"12","author":"Waters LI","year":"2007","unstructured":"WatersLI. 2007. 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