{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T04:43:45Z","timestamp":1791434625433,"version":"4.3.3"},"reference-count":37,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2022,11,16]],"date-time":"2022-11-16T00:00:00Z","timestamp":1668556800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100004319","name":"Pfizer","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004319","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004325","name":"AstraZeneca","doi-asserted-by":"publisher","award":["NCT02497781"],"award-info":[{"award-number":["NCT02497781"]}],"id":[{"id":"10.13039\/100004325","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004325","name":"AstraZeneca","doi-asserted-by":"publisher","award":["NCT02475733"],"award-info":[{"award-number":["NCT02475733"]}],"id":[{"id":"10.13039\/100004325","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004325","name":"AstraZeneca","doi-asserted-by":"publisher","award":["NCT01893346"],"award-info":[{"award-number":["NCT01893346"]}],"id":[{"id":"10.13039\/100004325","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006483","name":"AbbVie","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100006483","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clin Pharma and Therapeutics"],"published-print":{"date-parts":[[2023,1]]},"abstract":"<jats:p>Ceftazidime\u2010avibactam is a novel \u03b2\u2010lactam\/\u03b2\u2010lactamase inhibitor combination developed to treat serious Gram\u2010negative bacterial infections; approved indications include complicated urinary tract infection, complicated intra\u2010abdominal infection, and hospital\u2010acquired pneumonia including ventilator\u2010associated pneumonia in patients \u2265\u20093\u2009months old. Because of the predominantly renal clearance of ceftazidime and avibactam, dose adjustments (reductions) are required for patients with estimated creatinine clearance (CrCL) \u2264\u200950\u2009mL\/min. We describe the application of combined adult and pediatric population pharmacokinetic models in developing ceftazidime\u2010avibactam dose recommendations for pediatric patients \u2265\u20092 to &lt;\u200918\u2009years old with body surface area\u2010normalized CrCL \u2264\u200950\u2009mL\/min\/1.73\u2009m<jats:sup>2<\/jats:sup>, including moderate, severe, or very severe renal impairment, or end\u2010stage renal disease requiring hemodialysis, and for patients \u2265\u20093\u2009months to &lt;\u20092\u2009years old with mild, moderate, or severe renal impairment. Models included allometric scaling for all subjects and simulations (1,000 subjects per age group, renal function group, and indication) were performed nonparametrically using <jats:italic>post hoc<\/jats:italic> random effects. Doses were selected based on simulated pediatric patients achieving steady\u2010state exposures similar to adults and high probability of target attainment (using a simultaneous joint target for both ceftazidime and avibactam). Because there were few children with renal impairment in the ceftazidime\u2010avibactam clinical trials, selected pediatric doses were guided by extrapolation and matching of adult exposures associated with efficacy and within established safety margins. The recommended doses for pediatric patients with estimated CrCL \u2264\u200950\u2009mL\/min\/1.73\u2009m<jats:sup>2<\/jats:sup> use equivalent adjustments in dose quantity and\/or administration interval (vs. the corresponding age group with normal renal function) as those for adults.<\/jats:p>","DOI":"10.1002\/cpt.2764","type":"journal-article","created":{"date-parts":[[2022,10,14]],"date-time":"2022-10-14T12:50:01Z","timestamp":1665751801000},"page":"182-195","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Population Pharmacokinetic Modeling for Ceftazidime\u2010Avibactam Renal Dose Adjustments in Pediatric Patients 3\u2009months and Older"],"prefix":"10.1111","volume":"113","author":[{"given":"Richard","family":"Franzese","sequence":"first","affiliation":[{"name":"Certara Strategic Consulting  Raleigh North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Todd","family":"Riccobene","sequence":"additional","affiliation":[{"name":"AbbVie  Madison New Jersey USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy","family":"Carrothers","sequence":"additional","affiliation":[{"name":"AbbVie  Madison New Jersey USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manoli","family":"Vourvahis","sequence":"additional","affiliation":[{"name":"Pfizer  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erica","family":"Winter","sequence":"additional","affiliation":[{"name":"Pfizer  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"Lovern","sequence":"additional","affiliation":[{"name":"Certara Strategic Consulting  Raleigh North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lynn","family":"McFadyen","sequence":"additional","affiliation":[{"name":"Pfizer  Sandwich Kent UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,11,16]]},"reference":[{"key":"e_1_2_11_1_1","unstructured":"Pfizer.Summary of Product Characteristics: Zavicefta 2 g\/0.5 g powder for concentrate for solution for infusion<https:\/\/www.ema.europa.eu\/documents\/product\u2010information\/zavicefta\u2010epar\u2010product\u2010information_en.pdf>. Accessed September 7 2022."},{"key":"e_1_2_11_2_1","unstructured":"Allergan.AVYCAZ (ceftazidime and avibactam) for injection for intravenous use<https:\/\/www.allergan.com\/assets\/pdf\/avycaz_pi>. Accessed September 7 2022."},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1159\/000180580"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2008030287"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/cts.12585"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.02187-18"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.02105-19"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.02446-17"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpt.2460"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1097\/INF.0000000000002395"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00862-16"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1097\/INF.0000000000002392"},{"key":"e_1_2_11_13_1","unstructured":"International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use.E11(R1) \u2013 Addendum: Clinical Investigation of Medicinal Products in the Pediatric Population<https:\/\/database.ich.org\/sites\/default\/files\/E11_R1_Addendum.pdf>. Accessed September 7 2022."},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcph.744"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1111\/bcp.13809"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpt.1332"},{"issue":"1","key":"e_1_2_11_17_1","first-page":"S13","article-title":"Progress in drug development\u2010pediatric dose selection: workshop summary","volume":"61","author":"Wang J.","year":"2021","journal-title":"J. Clin. Pharmacol."},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00467-008-0997-5"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcph.793"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.25.5.638"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.2147\/CE.S40698"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.3390\/jcm10051068"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijantimicag.2011.09.012"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkp197"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkq161"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciac268"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciab1013"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/12.suppl_A.147"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.2165\/00003495-198529020-00002"},{"key":"e_1_2_11_30_1","unstructured":"US Food and Drug Administration.Leveraging existing clinical data for extrapolation to pediatric uses of medical devices. Guidance for Industry and Food and Drug Administration Staff<https:\/\/www.fda.gov\/regulatory\u2010information\/search\u2010fda\u2010guidance\u2010documents\/leveraging\u2010existing\u2010clinical\u2010data\u2010extrapolation\u2010pediatric\u2010uses\u2010medical\u2010devices>. Accessed September 7 2022."},{"key":"e_1_2_11_31_1","doi-asserted-by":"publisher","DOI":"10.1111\/bcp.13883"},{"key":"e_1_2_11_32_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40262-019-00813-w"},{"key":"e_1_2_11_33_1","doi-asserted-by":"publisher","DOI":"10.3390\/antibiotics11081007"},{"key":"e_1_2_11_34_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.02320-19"},{"key":"e_1_2_11_35_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40121-022-00682-0"},{"key":"e_1_2_11_36_1","doi-asserted-by":"publisher","DOI":"10.1111\/bcpt.13209"},{"key":"e_1_2_11_37_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.25.2.201"}],"container-title":["Clinical Pharmacology &amp; Therapeutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cpt.2764","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/cpt.2764","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cpt.2764","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,11,7]],"date-time":"2023-11-07T13:31:45Z","timestamp":1699363905000},"score":1,"resource":{"primary":{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/10.1002\/cpt.2764"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,11,16]]},"references-count":37,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2023,1]]}},"alternative-id":["10.1002\/cpt.2764"],"URL":"https:\/\/doi.org\/10.1002\/cpt.2764","archive":["Portico"],"relation":{},"ISSN":["0009-9236","1532-6535"],"issn-type":[{"value":"0009-9236","type":"print"},{"value":"1532-6535","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,11,16]]},"assertion":[{"value":"2022-05-19","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-10-02","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-11-16","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}