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<title>Pharmacokinetic Enhancers - LiverTox - NCBI Bookshelf</title>
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<meta name="robots" content="INDEX,FOLLOW,NOARCHIVE" /><meta name="citation_inbook_title" content="LiverTox: Clinical and Research Information on Drug-Induced Liver Injury [Internet]" /><meta name="citation_title" content="Pharmacokinetic Enhancers" /><meta name="citation_publisher" content="National Institute of Diabetes and Digestive and Kidney Diseases" /><meta name="citation_date" content="2017/08/17" /><meta name="citation_pmid" content="31643249" /><meta name="citation_fulltext_html_url" content="https://www.ncbi.nlm.nih.gov/books/NBK547913/" /><link rel="schema.DC" href="http://purl.org/DC/elements/1.0/" /><meta name="DC.Title" content="Pharmacokinetic Enhancers" /><meta name="DC.Type" content="Text" /><meta name="DC.Publisher" content="National Institute of Diabetes and Digestive and Kidney Diseases" /><meta name="DC.Date" content="2017/08/17" /><meta name="DC.Identifier" content="https://www.ncbi.nlm.nih.gov/books/NBK547913/" /><meta name="description" content="Pharmacokinetic enhancers or boosting agents are used in combination with a primary therapeutic agent, not for their direct effects on the disease or condition for which they are used, but because they enhance the activity, increase drug levels and/or prolong the half-life of the primary agent. Pharmacokinetic enhancers typically inhibit enzymes such as human cytochrome P450 (CYP 3A) and thereby block the rate-controlling steps in the metabolism of the primary drug or inhibit its inactivation. While pharmacokinetic enhancers are usually well tolerated, they can be problematic and may account for side effects including liver injury of the drug combination. Furthermore, pharmacokinetic enhancers are often used as a fixed combination with the primary agent in one tablet, capsule, powder or solution for injection. For this reason, their role in causing adverse events may be difficult to define unless there are direct comparisons to subjects treated with the primary agent alone." /><meta name="og:title" content="Pharmacokinetic Enhancers" /><meta name="og:type" content="book" /><meta name="og:description" content="Pharmacokinetic enhancers or boosting agents are used in combination with a primary therapeutic agent, not for their direct effects on the disease or condition for which they are used, but because they enhance the activity, increase drug levels and/or prolong the half-life of the primary agent. Pharmacokinetic enhancers typically inhibit enzymes such as human cytochrome P450 (CYP 3A) and thereby block the rate-controlling steps in the metabolism of the primary drug or inhibit its inactivation. While pharmacokinetic enhancers are usually well tolerated, they can be problematic and may account for side effects including liver injury of the drug combination. Furthermore, pharmacokinetic enhancers are often used as a fixed combination with the primary agent in one tablet, capsule, powder or solution for injection. For this reason, their role in causing adverse events may be difficult to define unless there are direct comparisons to subjects treated with the primary agent alone." /><meta name="og:url" content="https://www.ncbi.nlm.nih.gov/books/NBK547913/" /><meta name="og:site_name" content="NCBI Bookshelf" /><meta name="og:image" content="https://www.ncbi.nlm.nih.gov/corehtml/pmc/pmcgifs/bookshelf/thumbs/th-livertox-lrg.png" /><meta name="twitter:card" content="summary" /><meta name="twitter:site" content="@ncbibooks" /><meta name="bk-non-canon-loc" content="/books/n/livertox/PKEnhancers/" /><link rel="canonical" href="https://www.ncbi.nlm.nih.gov/books/NBK547913/" /><link rel="stylesheet" href="/corehtml/pmc/css/figpopup.css" type="text/css" media="screen" /><link rel="stylesheet" href="/corehtml/pmc/css/bookshelf/2.26/css/books.min.css" type="text/css" /><link rel="stylesheet" href="/corehtml/pmc/css/bookshelf/2.26/css/books_print.min.css" type="text/css" /><style type="text/css">p a.figpopup{display:inline !important} .bk_tt {font-family: monospace} .first-line-outdent .bk_ref {display: inline} </style><script type="text/javascript" src="/corehtml/pmc/js/jquery.hoverIntent.min.js"> </script><script type="text/javascript" src="/corehtml/pmc/js/common.min.js?_=3.18"> </script><script type="text/javascript">window.name="mainwindow";</script><script type="text/javascript" src="/corehtml/pmc/js/bookshelf/2.26/book-toc.min.js"> </script><script type="text/javascript" src="/corehtml/pmc/js/bookshelf/2.26/books.min.js"> </script>
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<div class="pre-content"><div><div class="bk_prnt"><p class="small">NCBI Bookshelf. A service of the National Library of Medicine, National Institutes of Health.</p><p>LiverTox: Clinical and Research Information on Drug-Induced Liver Injury [Internet]. Bethesda (MD): National Institute of Diabetes and Digestive and Kidney Diseases; 2012-. </p></div></div></div>
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<div class="main-content lit-style" itemscope="itemscope" itemtype="http://schema.org/CreativeWork"><div class="meta-content fm-sec"><h1 id="_NBK547913_"><span class="title" itemprop="name">Pharmacokinetic Enhancers</span></h1><p class="small">Last Update: <span itemprop="dateModified">August 17, 2017</span>.</p></div><div class="body-content whole_rhythm" itemprop="text"><div id="PKEnhancers.OVERVIEW"><h2 id="_PKEnhancers_OVERVIEW_">OVERVIEW</h2><p>Pharmacokinetic enhancers or boosting agents are used in combination with a primary therapeutic agent, not for their direct effects on the disease or condition for which they are used, but because they enhance the activity, increase drug levels and/or prolong the half-life of the primary agent. Pharmacokinetic enhancers typically inhibit enzymes such as human cytochrome P450 (CYP 3A) and thereby block the rate-controlling steps in the metabolism of the primary drug or inhibit its inactivation. While pharmacokinetic enhancers are usually well tolerated, they can be problematic and may account for side effects including liver injury of the drug combination. Furthermore, pharmacokinetic enhancers are often used as a fixed combination with the primary agent in one tablet, capsule, powder or solution for injection. For this reason, their role in causing adverse events may be difficult to define unless there are direct comparisons to subjects treated with the primary agent alone.</p><p>Pharmacokinetic enhancers in current use can be categorized into three groups: (1) beta-lactamase inhibitors used in combination with beta-lactam antibiotics such as the penicillins and cephalosporins (clavulanate, tazobactam, sulbactam, avibactam); (2) broad-spectrum inhibitors of hepatic drug-metabolizing enzymes such as CYP 3A4 (ritonavir, cobicistat); and (3) inhibitors of drug-specific metabolizing enzymes (carbidopa, cilastatin, tipiracil). Undoubtedly, other categories of pharmacokinetic enhancers will be developed as they can play an essential role in optimizing pharmacologic and therapeutic effects of important medications.</p><p>The major pharmacokinetic enhancers in clinical use in the United States are listed in the table below, along with the primary agent(s) with which they are combined, major brand name(s) of the combination, the enzyme activity that they inhibit or enhance, year of approval, and the hepatotoxicity score of the combination. Specific information and references to their hepatotoxicity are given in the sections on the primary agents rather than separately for the pharmacokinetic enhancer.</p><div id="PKEnhancers.Tc" class="table"><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK547913/table/PKEnhancers.Tc/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__PKEnhancers.Tc_lrgtbl__"><table><thead><tr><th id="hd_h_PKEnhancers.Tc_1_1_1_1" colspan="6" scope="colgroup" rowspan="1" style="text-align:left;vertical-align:top;">PHARMACOKINETIC ENHANCERS (2017)</th></tr><tr><th headers="hd_h_PKEnhancers.Tc_1_1_1_1" id="hd_h_PKEnhancers.Tc_1_1_2_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Pharmacokinetic Enhancer</th><th headers="hd_h_PKEnhancers.Tc_1_1_1_1" id="hd_h_PKEnhancers.Tc_1_1_2_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Primary Agent</th><th headers="hd_h_PKEnhancers.Tc_1_1_1_1" id="hd_h_PKEnhancers.Tc_1_1_2_3" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Brand Name</th><th headers="hd_h_PKEnhancers.Tc_1_1_1_1" id="hd_h_PKEnhancers.Tc_1_1_2_4" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Enzyme Inhibited</th><th headers="hd_h_PKEnhancers.Tc_1_1_1_1" id="hd_h_PKEnhancers.Tc_1_1_2_5" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Year Approved</th><th headers="hd_h_PKEnhancers.Tc_1_1_1_1" id="hd_h_PKEnhancers.Tc_1_1_2_6" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Likelihood Score†</th></tr></thead><tbody><tr><td headers="hd_h_PKEnhancers.Tc_1_1_1_1 hd_h_PKEnhancers.Tc_1_1_2_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Carbidopa</td><td headers="hd_h_PKEnhancers.Tc_1_1_1_1 hd_h_PKEnhancers.Tc_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Levodopa</td><td headers="hd_h_PKEnhancers.Tc_1_1_1_1 hd_h_PKEnhancers.Tc_1_1_2_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Sinemet</td><td headers="hd_h_PKEnhancers.Tc_1_1_1_1 hd_h_PKEnhancers.Tc_1_1_2_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">L-amino acid decarboxylase</td><td headers="hd_h_PKEnhancers.Tc_1_1_1_1 hd_h_PKEnhancers.Tc_1_1_2_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">1975</td><td headers="hd_h_PKEnhancers.Tc_1_1_1_1 hd_h_PKEnhancers.Tc_1_1_2_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">E</td></tr><tr><td headers="hd_h_PKEnhancers.Tc_1_1_1_1 hd_h_PKEnhancers.Tc_1_1_2_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Clavulanic acid</td><td headers="hd_h_PKEnhancers.Tc_1_1_1_1 hd_h_PKEnhancers.Tc_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Amoxicillin</td><td headers="hd_h_PKEnhancers.Tc_1_1_1_1 hd_h_PKEnhancers.Tc_1_1_2_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Augmentin</td><td headers="hd_h_PKEnhancers.Tc_1_1_1_1 hd_h_PKEnhancers.Tc_1_1_2_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Beta-lactamase</td><td headers="hd_h_PKEnhancers.Tc_1_1_1_1 hd_h_PKEnhancers.Tc_1_1_2_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">1984</td><td headers="hd_h_PKEnhancers.Tc_1_1_1_1 hd_h_PKEnhancers.Tc_1_1_2_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">A*</td></tr><tr><td headers="hd_h_PKEnhancers.Tc_1_1_1_1 hd_h_PKEnhancers.Tc_1_1_2_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Clavulanic acid</td><td headers="hd_h_PKEnhancers.Tc_1_1_1_1 hd_h_PKEnhancers.Tc_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Ticarcillin</td><td headers="hd_h_PKEnhancers.Tc_1_1_1_1 hd_h_PKEnhancers.Tc_1_1_2_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Timentin</td><td headers="hd_h_PKEnhancers.Tc_1_1_1_1 hd_h_PKEnhancers.Tc_1_1_2_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Beta-lactamase</td><td headers="hd_h_PKEnhancers.Tc_1_1_1_1 hd_h_PKEnhancers.Tc_1_1_2_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">1985</td><td headers="hd_h_PKEnhancers.Tc_1_1_1_1 hd_h_PKEnhancers.Tc_1_1_2_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">A*</td></tr><tr><td headers="hd_h_PKEnhancers.Tc_1_1_1_1 hd_h_PKEnhancers.Tc_1_1_2_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Tazobactam</td><td headers="hd_h_PKEnhancers.Tc_1_1_1_1 hd_h_PKEnhancers.Tc_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Piperacillin</td><td headers="hd_h_PKEnhancers.Tc_1_1_1_1 hd_h_PKEnhancers.Tc_1_1_2_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Zosyn</td><td headers="hd_h_PKEnhancers.Tc_1_1_1_1 hd_h_PKEnhancers.Tc_1_1_2_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Beta-lactamase</td><td headers="hd_h_PKEnhancers.Tc_1_1_1_1 hd_h_PKEnhancers.Tc_1_1_2_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">1985</td><td headers="hd_h_PKEnhancers.Tc_1_1_1_1 hd_h_PKEnhancers.Tc_1_1_2_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">E*</td></tr><tr><td headers="hd_h_PKEnhancers.Tc_1_1_1_1 hd_h_PKEnhancers.Tc_1_1_2_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Cilastatin</td><td headers="hd_h_PKEnhancers.Tc_1_1_1_1 hd_h_PKEnhancers.Tc_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Imipenem</td><td headers="hd_h_PKEnhancers.Tc_1_1_1_1 hd_h_PKEnhancers.Tc_1_1_2_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Primaxin</td><td headers="hd_h_PKEnhancers.Tc_1_1_1_1 hd_h_PKEnhancers.Tc_1_1_2_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Dehydropeptidase 1</td><td headers="hd_h_PKEnhancers.Tc_1_1_1_1 hd_h_PKEnhancers.Tc_1_1_2_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">1985</td><td headers="hd_h_PKEnhancers.Tc_1_1_1_1 hd_h_PKEnhancers.Tc_1_1_2_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">D</td></tr><tr><td headers="hd_h_PKEnhancers.Tc_1_1_1_1 hd_h_PKEnhancers.Tc_1_1_2_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Sulbactam</td><td headers="hd_h_PKEnhancers.Tc_1_1_1_1 hd_h_PKEnhancers.Tc_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Ampicillin</td><td headers="hd_h_PKEnhancers.Tc_1_1_1_1 hd_h_PKEnhancers.Tc_1_1_2_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Unasyn</td><td headers="hd_h_PKEnhancers.Tc_1_1_1_1 hd_h_PKEnhancers.Tc_1_1_2_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Beta-lactamase</td><td headers="hd_h_PKEnhancers.Tc_1_1_1_1 hd_h_PKEnhancers.Tc_1_1_2_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">1986</td><td headers="hd_h_PKEnhancers.Tc_1_1_1_1 hd_h_PKEnhancers.Tc_1_1_2_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">C</td></tr><tr><td headers="hd_h_PKEnhancers.Tc_1_1_1_1 hd_h_PKEnhancers.Tc_1_1_2_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Ritonavir‡</td><td headers="hd_h_PKEnhancers.Tc_1_1_1_1 hd_h_PKEnhancers.Tc_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Lopinavir</td><td headers="hd_h_PKEnhancers.Tc_1_1_1_1 hd_h_PKEnhancers.Tc_1_1_2_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Kaletra</td><td headers="hd_h_PKEnhancers.Tc_1_1_1_1 hd_h_PKEnhancers.Tc_1_1_2_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">CYP 3A4</td><td headers="hd_h_PKEnhancers.Tc_1_1_1_1 hd_h_PKEnhancers.Tc_1_1_2_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">1996</td><td headers="hd_h_PKEnhancers.Tc_1_1_1_1 hd_h_PKEnhancers.Tc_1_1_2_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">D</td></tr><tr><td headers="hd_h_PKEnhancers.Tc_1_1_1_1 hd_h_PKEnhancers.Tc_1_1_2_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Ritonavir‡</td><td headers="hd_h_PKEnhancers.Tc_1_1_1_1 hd_h_PKEnhancers.Tc_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Paritaprevir</td><td headers="hd_h_PKEnhancers.Tc_1_1_1_1 hd_h_PKEnhancers.Tc_1_1_2_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Viekira Pak</td><td headers="hd_h_PKEnhancers.Tc_1_1_1_1 hd_h_PKEnhancers.Tc_1_1_2_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">CYP 3A4</td><td headers="hd_h_PKEnhancers.Tc_1_1_1_1 hd_h_PKEnhancers.Tc_1_1_2_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">2015</td><td headers="hd_h_PKEnhancers.Tc_1_1_1_1 hd_h_PKEnhancers.Tc_1_1_2_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">E*</td></tr><tr><td headers="hd_h_PKEnhancers.Tc_1_1_1_1 hd_h_PKEnhancers.Tc_1_1_2_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Cobicistat‡‡</td><td headers="hd_h_PKEnhancers.Tc_1_1_1_1 hd_h_PKEnhancers.Tc_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Elvitegravir</td><td headers="hd_h_PKEnhancers.Tc_1_1_1_1 hd_h_PKEnhancers.Tc_1_1_2_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Stribild, Genvoya</td><td headers="hd_h_PKEnhancers.Tc_1_1_1_1 hd_h_PKEnhancers.Tc_1_1_2_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">CYP 3A4</td><td headers="hd_h_PKEnhancers.Tc_1_1_1_1 hd_h_PKEnhancers.Tc_1_1_2_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">2012</td><td headers="hd_h_PKEnhancers.Tc_1_1_1_1 hd_h_PKEnhancers.Tc_1_1_2_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">E</td></tr><tr><td headers="hd_h_PKEnhancers.Tc_1_1_1_1 hd_h_PKEnhancers.Tc_1_1_2_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Cobicistat‡‡</td><td headers="hd_h_PKEnhancers.Tc_1_1_1_1 hd_h_PKEnhancers.Tc_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Atazanavir</td><td headers="hd_h_PKEnhancers.Tc_1_1_1_1 hd_h_PKEnhancers.Tc_1_1_2_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Evotaz</td><td headers="hd_h_PKEnhancers.Tc_1_1_1_1 hd_h_PKEnhancers.Tc_1_1_2_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">CYP 3A4</td><td headers="hd_h_PKEnhancers.Tc_1_1_1_1 hd_h_PKEnhancers.Tc_1_1_2_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">2015</td><td headers="hd_h_PKEnhancers.Tc_1_1_1_1 hd_h_PKEnhancers.Tc_1_1_2_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">D</td></tr><tr><td headers="hd_h_PKEnhancers.Tc_1_1_1_1 hd_h_PKEnhancers.Tc_1_1_2_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Cobicistat‡‡</td><td headers="hd_h_PKEnhancers.Tc_1_1_1_1 hd_h_PKEnhancers.Tc_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Darunavir</td><td headers="hd_h_PKEnhancers.Tc_1_1_1_1 hd_h_PKEnhancers.Tc_1_1_2_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Prezcobix</td><td headers="hd_h_PKEnhancers.Tc_1_1_1_1 hd_h_PKEnhancers.Tc_1_1_2_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">CYP 3A4</td><td headers="hd_h_PKEnhancers.Tc_1_1_1_1 hd_h_PKEnhancers.Tc_1_1_2_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">2015</td><td headers="hd_h_PKEnhancers.Tc_1_1_1_1 hd_h_PKEnhancers.Tc_1_1_2_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">E*</td></tr><tr><td headers="hd_h_PKEnhancers.Tc_1_1_1_1 hd_h_PKEnhancers.Tc_1_1_2_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Tipiracil</td><td headers="hd_h_PKEnhancers.Tc_1_1_1_1 hd_h_PKEnhancers.Tc_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Trifluridine</td><td headers="hd_h_PKEnhancers.Tc_1_1_1_1 hd_h_PKEnhancers.Tc_1_1_2_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Lonsurf</td><td headers="hd_h_PKEnhancers.Tc_1_1_1_1 hd_h_PKEnhancers.Tc_1_1_2_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Thymidine phosphorylase</td><td headers="hd_h_PKEnhancers.Tc_1_1_1_1 hd_h_PKEnhancers.Tc_1_1_2_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">2015</td><td headers="hd_h_PKEnhancers.Tc_1_1_1_1 hd_h_PKEnhancers.Tc_1_1_2_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">E</td></tr><tr><td headers="hd_h_PKEnhancers.Tc_1_1_1_1 hd_h_PKEnhancers.Tc_1_1_2_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Avibactam</td><td headers="hd_h_PKEnhancers.Tc_1_1_1_1 hd_h_PKEnhancers.Tc_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Ceftazidime</td><td headers="hd_h_PKEnhancers.Tc_1_1_1_1 hd_h_PKEnhancers.Tc_1_1_2_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Ayvcaz</td><td headers="hd_h_PKEnhancers.Tc_1_1_1_1 hd_h_PKEnhancers.Tc_1_1_2_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Beta-lactamase</td><td headers="hd_h_PKEnhancers.Tc_1_1_1_1 hd_h_PKEnhancers.Tc_1_1_2_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">2015</td><td headers="hd_h_PKEnhancers.Tc_1_1_1_1 hd_h_PKEnhancers.Tc_1_1_2_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">E</td></tr></tbody></table></div></div><p>† The likelihood score is for the combination, as the role of the primary agent vs the pharmacokinetic enhancer cannot always be clearly demarcated. In the case of clavulanic acid, it is usually considered the primary cause of the liver injury rather than amoxicillin or ticarcillin with which it is combined.</p><p>‡ Ritonavir is a HIV-protease inhibitor and has independent activity against HIV infection, but is used commonly to “boost” levels of other drugs active against HIV or HCV that are metabolized by CYP 3A4 and thus achieve higher and more prolonged levels when combined with ritonavir.</p><p>‡‡ Cobicistat inhibits several drug-metabolizing enzymes including CYP 3A4, CYP 2D6 and the P-glycoprotein transporter, but has no antiviral activity on its own.</p><div id="PKEnhancers.Pharmacokinetic_Enhancers_Co"><h3>Pharmacokinetic Enhancers Combined with Specific Primary Agent(s):</h3><p>Avibactam [<a href="/books/n/livertox/Cephalosporins/">Ceftazidime</a>], Carbidopa [<a href="/books/n/livertox/LevodopaCarbodopa/">Levodopa</a>], Cilastatin [<a href="/books/n/livertox/Imipenemcilastatin/">Imipenem</a>], Clavulanic Acid [<a href="/books/n/livertox/AmoxicillinClavulana/">Amoxicillin</a>, <a href="/books/n/livertox/TicarcillinClavulana/">Ticarcillin</a>], Cobicistat [<a href="/books/n/livertox/Atazanavir/">Atazanavir</a>, <a href="/books/n/livertox/Darunavir/">Darunavir</a>, <a href="/books/n/livertox/Elvitegravir_Cobicis/">Elvitegravir</a>], Ritonavir [<a href="/books/n/livertox/Lopinavir/">Lopinavir</a>, <a href="/books/n/livertox/ViekiraPak/">Paritaprevir</a>], Sulbactam [<a href="/books/n/livertox/AmpicillinSulbactam/">Ampicillin</a>], Tazobactam [<a href="/books/n/livertox/PiperacillinTazob/">Piperacillin</a>], Tipiracil [<a href="/books/n/livertox/Trifluridine/">Trifluridine</a>]</p></div></div><div id="bk_toc_contnr"></div></div></div>
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