{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T14:34:17Z","timestamp":1791988457526,"version":"4.4.0"},"reference-count":29,"publisher":"The Pediatric Pharmacy Association","issue":"6","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020]]},"abstract":"<jats:sec>\n          <jats:title>OBJECTIVES<\/jats:title>\n          <jats:p>Aprepitant is effective for the prevention of chemotherapy-induced or postoperative nausea and vomiting (CINV\/PONV). The aim of this study was to develop a population pharmacokinetic (PK) model of aprepitant in pediatric patients and to support dosing recommendations for oral aprepitant in pediatric patients at risk of CINV.<\/jats:p>\n        <\/jats:sec>\n        <jats:sec>\n          <jats:title>METHODS<\/jats:title>\n          <jats:p>A population PK model was constructed based on data from 3 clinical studies in which children (6 months to 12 years) and adolescents (12\u201319 years) were treated with a 3-day regimen of oral aprepitant (capsules or suspension), with or without intravenous fosaprepitant on day 1 (CINV), or a single dose of oral aprepitant (capsules or suspension; PONV). Nonlinear mixed-effects modeling was used for model development, and a stepwise covariate search determined factors influencing PK parameters. Simulations were performed to guide final dosing strategies of aprepitant in pediatric patients.<\/jats:p>\n        <\/jats:sec>\n        <jats:sec>\n          <jats:title>RESULTS<\/jats:title>\n          <jats:p>The analysis included 1326 aprepitant plasma concentrations from 147 patients. Aprepitant PK was described by a 2-compartment model with linear elimination and first-order absorption, with allometric scaling for central and peripheral clearance and volume using body weight, and a cytochrome P450 3A4 maturation component for the effect of ontogeny on systemic clearance. Simulations established that application of a weight-based (for those &lt;12 years) and fixed-dose (for those 12\u201317 years) dosing regimen results in comparable exposures to those observed in adults.<\/jats:p>\n        <\/jats:sec>\n        <jats:sec>\n          <jats:title>CONCLUSIONS<\/jats:title>\n          <jats:p>The developed population PK model adequately described aprepitant PK across a broad pediatric population, justifying fixed (adult) dosing for adolescents and weight-based dosing of oral aprepitant for children.<\/jats:p>\n        <\/jats:sec>","DOI":"10.5863\/1551-6776-25.6.528","type":"journal-article","created":{"date-parts":[[2020,8,14]],"date-time":"2020-08-14T15:06:28Z","timestamp":1597417588000},"page":"528-539","source":"Crossref","is-referenced-by-count":1,"title":["Modeling and Simulation Analysis of Aprepitant Pharmacokinetics in Pediatric Patients With Postoperative or Chemotherapy-Induced Nausea and Vomiting"],"prefix":"10.5863","volume":"25","author":[{"given":"Anne","family":"Chain","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebecca","family":"Wrishko","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Grygoriy","family":"Vasilinin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samer","family":"Mouksassi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"3883","reference":[{"issue":"5","key":"i1551-6776-25-6-528-b1","series-title":"Supportive Care Cancer","first-page":"497","article-title":"Chemotherapy-induced nausea and vomiting: incidence and impact on patient quality of life at community oncology settings","volume":"15","year":"2007","unstructured":"Cohen\n              L\n            , de MoorCA, EisenbergP, \n          et al. Chemotherapy-induced nausea and vomiting: incidence and impact on patient quality of life at community oncology settings. Supportive Care Cancer. 2007;15(5):497\u2013503."},{"issue":"3","key":"i1551-6776-25-6-528-b2","series-title":"Anesth Analg","first-page":"652","article-title":"Which clinical anesthesia outcomes are important to avoid? The perspective of patients","volume":"89","year":"1999","unstructured":"Macario\n              A\n            , WeingerM, CarneyS, KimA.\n          Which clinical anesthesia outcomes are important to avoid? The perspective of patients. Anesth Analg. 1999;89(3):652\u2013658."},{"issue":"11","key":"i1551-6776-25-6-528-b3","series-title":"J Clin Oncol","first-page":"1746","article-title":"The influence of symptoms of disease and side effects of treatment on compliance with cancer therapy","volume":"6","year":"1988","unstructured":"Richardson\n              JL\n            , MarksG, LevineA.\n          The influence of symptoms of disease and side effects of treatment on compliance with cancer therapy. J Clin Oncol. 1988;6(11):1746\u20131752."},{"issue":"4","key":"i1551-6776-25-6-528-b4","series-title":"Cancer","first-page":"931","article-title":"Acute and delayed nausea and emesis control in pediatric oncology patients","volume":"106","year":"2006","unstructured":"Holdsworth\n              MT\n            , RaischDW, FrostJ.\n          Acute and delayed nausea and emesis control in pediatric oncology patients. Cancer. 2006;106(4):931\u2013940."},{"key":"i1551-6776-25-6-528-b5","series-title":"MASCC\/ESMO Antiemetic Guideline 2016 (with updates in 2019) V.1.5.","year":"2019","unstructured":"Multinational Association of Supportive Care in Cancer.\n          \n          MASCC\/ESMO Antiemetic Guideline 2016 (with updates in 2019) V.1.5.\n          2019. Accessed July 16, 2020. https:\/\/www.mascc.org\/assets\/Guidelines-Tools\/mascc_anti-emetic_guidelines_english_v.1.5SEPT29.2019.pdf"},{"key":"i1551-6776-25-6-528-b6","series-title":"Emend [package insert]","year":"2019","unstructured":"Emend [package insert]. Whitehouse Station, NJ: Merck Sharpe & Dohme Corp; September2019."},{"key":"i1551-6776-25-6-528-b7","article-title":"Emend [summary of product characteristics]","year":"2017","unstructured":"Emend [summary of product characteristics]. Hertford-shire, UK: Merck Sharp & Dohme Ltd; 2017."},{"issue":"10","key":"i1551-6776-25-6-528-b8","series-title":"Expert Opin Drug Metab Toxicol","first-page":"1277","article-title":"Pharmacokinetic evaluation of fosaprepitant dimeglumine","volume":"6","year":"2010","unstructured":"Colon-Gonzalez\n              F\n            , KraftWK.\n          Pharmacokinetic evaluation of fosaprepitant dimeglumine. Expert Opin Drug Metab Toxicol. 2010;6(10):1277\u20131286."},{"key":"i1551-6776-25-6-528-b9","article-title":"Emend [package insert]","year":"2017","unstructured":"Emend [package insert]. Whitehouse Station, NJ: Merck Sharpe & Dohme Corp.; 2017."},{"key":"i1551-6776-25-6-528-b10","series-title":"IV Emend [summary of product characteristics]","year":"2017","unstructured":"IV Emend [summary of product characteristics]. Hertfordshire, UK: Merck Sharp & Dohme Ltd.; 2017."},{"issue":"7","key":"i1551-6776-25-6-528-b11","series-title":"J Clin Pharmacol","first-page":"834","article-title":"Tolerability of fosaprepitant and bioequivalency to aprepitant in healthy subjects","volume":"47","year":"2007","unstructured":"Lasseter\n              KC\n            , GambaleJ, JinB, \n          et al. Tolerability of fosaprepitant and bioequivalency to aprepitant in healthy subjects. J Clin Pharmacol. 2007;47(7):834\u2013840."},{"issue":"3","key":"i1551-6776-25-6-528-b12","series-title":"J Clin Pharmacol","first-page":"291","article-title":"Pharmacokinetics of aprepitant after single and multiple oral doses in healthy volunteers","volume":"46","year":"2006","unstructured":"Majumdar\n              AK\n            , HowardL, GoldbergMR, \n          et al. Pharmacokinetics of aprepitant after single and multiple oral doses in healthy volunteers. J Clin Pharmacol. 2006;46(3):291\u2013300."},{"issue":"2","key":"i1551-6776-25-6-528-b13","series-title":"Pediatr Blood Cancer","first-page":"242","article-title":"Aprepitant in adolescent patients for prevention of chemotherapy-induced nausea and vomiting: a randomized, double-blind, placebo-controlled study of efficacy and tolerability","volume":"52","year":"2009","unstructured":"Gore\n              L\n            , ChawlaS, PetrilliA, \n          et al. Aprepitant in adolescent patients for prevention of chemotherapy-induced nausea and vomiting: a randomized, double-blind, placebo-controlled study of efficacy and tolerability. Pediatr Blood Cancer. 2009;52(2):242\u2013247."},{"key":"i1551-6776-25-6-528-b14","unstructured":"A Study of MK-0869 (Aprepitant) and MK-0517 (Fosaprepitant) in Pediatric Participants Receiving Chemotherapy (MK-0869-134). ClinicalTrials.gov.identifier: NCT00818259. Updated September 25, 2018. Accessed July 16, 2020. https:\/\/clinicaltrials.gov\/ct2\/show\/NCT00818259"},{"key":"i1551-6776-25-6-528-b15","unstructured":"A Study of Aprepitant (MK-0869) in Pediatric Participants Undergoing Surgery (MK-0869-148). ClinicalTrials.gov. identifier: NCT00819039. Updated June 2, 2017. Accessed July 16, 2020. https:\/\/clinicaltrials.gov\/ct2\/show\/NCT00819039."},{"issue":"5","key":"i1551-6776-25-6-528-b16","series-title":"J Pharm Biomed Anal","first-page":"1213","article-title":"Simultaneous determination of aprepitant and two metabolites in human plasma by high-performance liquid chromatography with tandem mass spectrometric detection","volume":"35","year":"2004","unstructured":"Chavez-Eng\n              CM\n            , ConstanzerML, MatuszewskiBK.\n          Simultaneous determination of aprepitant and two metabolites in human plasma by high-performance liquid chromatography with tandem mass spectrometric detection. J Pharm Biomed Anal. 2004;35(5):1213\u20131229."},{"issue":"4","key":"i1551-6776-25-6-528-b17","series-title":"Br J Clin Pharmacol","first-page":"511","article-title":"Population pharmacokinetics and dose simulation of carvedilol in paediatric patients with congestive heart failure","volume":"65","year":"2008","unstructured":"Albers\n              S\n            , MeibohmB, MirTS, LaerS.\n          Population pharmacokinetics and dose simulation of carvedilol in paediatric patients with congestive heart failure. Br J Clin Pharmacol. 2008;65(4):511\u2013522."},{"issue":"9","key":"i1551-6776-25-6-528-b18","series-title":"Clin Pharmacokinet","first-page":"931","article-title":"Prediction of the clearance of eleven drugs and associated variability in neonates, infants and children","volume":"45","year":"2006","unstructured":"Johnson\n              TN\n            , Rostami-HodjeganA, TuckerGT.\n          Prediction of the clearance of eleven drugs and associated variability in neonates, infants and children. Clin Pharmacokinet. 2006;45(9):931\u2013956."},{"issue":"2","key":"i1551-6776-25-6-528-b19","series-title":"CPT Pharmacometrics Syst Pharmacol","first-page":"87","article-title":"Model evaluation of continuous data pharmacometric models: metrics and graphics","volume":"6","year":"2017","unstructured":"Nguyen\n              TH\n            , MouksassiMS, HolfordN, \n          et al. Model evaluation of continuous data pharmacometric models: metrics and graphics. CPT Pharmacometrics Syst Pharmacol. 2017;6(2):87\u2013109."},{"issue":"10","key":"i1551-6776-25-6-528-b20","series-title":"J Clin Pharmacol","first-page":"1601","article-title":"Clarification on precision criteria to derive sample size when designing pediatric pharmacokinetic studies","volume":"52","year":"2012","unstructured":"Wang\n              Y\n            , JadhavPR, LalaM, GobburuJV.\n          Clarification on precision criteria to derive sample size when designing pediatric pharmacokinetic studies. J Clin Pharmacol. 2012;52(10):1601\u20131606."},{"issue":"5\u20136","key":"i1551-6776-25-6-528-b21","series-title":"Eur J Clin Pharmacol","first-page":"341","article-title":"Effect of aprepitant on the pharmacokinetics and pharmacodynamics of warfarin","volume":"61","year":"2005","unstructured":"Depre\n              M\n            , Van HeckenA, OeyenM, \n          et al. Effect of aprepitant on the pharmacokinetics and pharmacodynamics of warfarin. Eur J Clin Pharmacol. 2005;61(5\u20136):341\u2013346."},{"issue":"6","key":"i1551-6776-25-6-528-b22","series-title":"Cancer Chemother Pharmacol","first-page":"609","article-title":"Lack of effect of aprepitant on the pharmacokinetics of docetaxel in cancer patients","volume":"55","year":"2005","unstructured":"Nygren\n              P\n            , HandeK, PettyKJ, \n          et al. Lack of effect of aprepitant on the pharmacokinetics of docetaxel in cancer patients. Cancer Chemother Pharmacol. 2005;55(6):609\u2013616."},{"issue":"11","key":"i1551-6776-25-6-528-b23","series-title":"Drug Metab Dispos","first-page":"1287","article-title":"Cytochrome P450 3A4 is the major enzyme involved in the metabolism of the substance P receptor antagonist aprepitant","volume":"32","year":"2004","unstructured":"Sanchez\n              RI\n            , WangRW, NewtonDJ, \n          et al. Cytochrome P450 3A4 is the major enzyme involved in the metabolism of the substance P receptor antagonist aprepitant. Drug Metab Dispos. 2004;32(11):1287\u20131292."},{"key":"i1551-6776-25-6-528-b24","article-title":"Office of Clinical Pharmacology review NDA 21\u2013957","year":"2008","unstructured":"Estes\n              K\n            , LeeSC, MehrotraN.\n          Office of Clinical Pharmacology review NDA 21\u2013957. December18, 2008. Silver Spring, MD: US Food and Drug Administration."},{"issue":"4","key":"i1551-6776-25-6-528-b25","series-title":"Lancet Oncol","first-page":"385","article-title":"Aprepitant for the prevention of chemotherapy-induced nausea and vomiting in children: a randomised, double-blind, phase 3 trial","volume":"16","year":"2015","unstructured":"Kang\n              HJ\n            , LoftusS, TaylorA, \n          et al. Aprepitant for the prevention of chemotherapy-induced nausea and vomiting in children: a randomised, double-blind, phase 3 trial. Lancet Oncol. 2015;16(4):385\u2013394."},{"issue":"1","key":"i1551-6776-25-6-528-b26","series-title":"Am J Cancer","first-page":"35","article-title":"The oral NK1 antagonist aprepitant for prevention of nausea and vomiting in patients receiving highly emetogenic chemotherapy: a review","volume":"4","year":"2005","unstructured":"de Wit\n              R\n            , HeskethPJ, WarrD.\n          The oral NK1 antagonist aprepitant for prevention of nausea and vomiting in patients receiving highly emetogenic chemotherapy: a review. Am J Cancer. 2005;4(1):35\u201348."},{"issue":"22","key":"i1551-6776-25-6-528-b27","series-title":"J Clin Oncol","first-page":"4112","article-title":"The oral neurokinin-1 antagonist aprepitant for the prevention of chemotherapy-induced nausea and vomiting: a multinational, randomized, double-blind, placebo-controlled trial in patients receiving high-dose cisplatin\u2014the Aprepitant Protocol 052 Study Group","volume":"21","year":"2003","unstructured":"Hesketh\n              PJ\n            , GrunbergSM, GrallaRJ, \n          et al. The oral neurokinin-1 antagonist aprepitant for the prevention of chemotherapy-induced nausea and vomiting: a multinational, randomized, double-blind, placebo-controlled trial in patients receiving high-dose cisplatin\u2014the Aprepitant Protocol 052 Study Group. J Clin Oncol. 2003;21(22):4112\u20134119."},{"issue":"12","key":"i1551-6776-25-6-528-b28","series-title":"Cancer","first-page":"3090","article-title":"Addition of the neurokinin 1 receptor antagonist aprepitant to standard antiemetic therapy improves control of chemotherapy-induced nausea and vomiting. Results from a randomized, double-blind, placebo-controlled trial in Latin America","volume":"97","year":"2003","unstructured":"Poli-Bigelli\n              S\n            , Rodrigues-PereiraJ, CaridesAD, \n          et al. Addition of the neurokinin 1 receptor antagonist aprepitant to standard antiemetic therapy improves control of chemotherapy-induced nausea and vomiting. Results from a randomized, double-blind, placebo-controlled trial in Latin America. Cancer. 2003;97(12):3090\u20133098."},{"issue":"6","key":"i1551-6776-25-6-528-b29","series-title":"Ann Oncol","first-page":"1000","article-title":"Comparison of an aprepitant regimen with a multiple-day ondansetron regimen, both with dexamethasone, for antiemetic efficacy in high-dose cisplatin treatment","volume":"17","year":"2006","unstructured":"Schmoll\n              HJ\n            , AaproMS, Poli-BigelliS, \n          et al. Comparison of an aprepitant regimen with a multiple-day ondansetron regimen, both with dexamethasone, for antiemetic efficacy in high-dose cisplatin treatment. Ann Oncol. 2006;17(6):1000\u20131006."}],"container-title":["The Journal of Pediatric Pharmacology and Therapeutics"],"original-title":[],"link":[{"URL":"https:\/\/jppt.kglmeridian.com\/view\/journals\/jppt\/25\/6\/article-p528.xml","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/meridian.allenpress.com\/jppt\/article-pdf\/25\/6\/528\/2585611\/1551-6776-25_6_528.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/jppt.kglmeridian.com\/downloadpdf\/journals\/jppt\/25\/6\/article-p528.xml","content-type":"text\/html","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/jppt.kglmeridian.com\/downloadpdf\/journals\/jppt\/25\/6\/article-p528.xml","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,5,16]],"date-time":"2025-05-16T00:39:30Z","timestamp":1747355970000},"score":1,"resource":{"primary":{"URL":"https:\/\/jppt.kglmeridian.com\/view\/journals\/jppt\/25\/6\/article-p528.xml"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020]]},"references-count":29,"journal-issue":{"issue":"6"},"URL":"https:\/\/doi.org\/10.5863\/1551-6776-25.6.528","relation":{},"ISSN":["1551-6776"],"issn-type":[{"value":"1551-6776","type":"print"}],"subject":[],"published":{"date-parts":[[2020]]}}}