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This population pharmacokinetic analysis used pooled plasma nirmatrelvir concentrations from eight completed phase I and II\/III studies to characterize nirmatrelvir pharmacokinetics when coadministered with ritonavir in adults with\/without COVID\u201019. Influence of covariates (e.g., formulation, dose, COVID\u201019) was examined using a stepwise forward selection (\u03b1\u2009=\u20090.05) and backward elimination (\u03b1\u2009=\u20090.001) approach. Simulations with 5000 subjects for each age and weight group and renal function category were performed to support dosing recommendations of nirmatrelvir\/ritonavir for adults with COVID\u201019 and guide dose adjustments for specific patient populations (e.g., renal insufficiency, pediatrics). The final model was a two\u2010compartment model with first\u2010order absorption, including allometric scaling of body weight and dose\u2010dependent absorption (power function on relative bioavailability). Nirmatrelvir clearance (CL) increased proportionally to body surface area\u2013normalized creatinine CL (nCLCR) up to 70\u2009ml\/min\/1.73\u2009m<jats:sup>2<\/jats:sup> and was independent of nCLCR above the breakpoint. Significant covariates included carbamazepine or itraconazole coadministration as markers for drug interactions, COVID\u201019 on CL, formulation on relative bioavailability, and age on central volume of distribution. Simulation results support current dosing recommendations of nirmatrelvir\/ritonavir 300\/100\u2009mg twice daily (b.i.d.) in adults with normal renal function or mild impairment and pediatrics (12 to &lt;18\u2009years) weighing \u226540\u2009kg and nirmatrelvir\/ritonavir 150\/100\u2009mg b.i.d. in adults with moderate renal impairment.<\/jats:p>","DOI":"10.1002\/psp4.13039","type":"journal-article","created":{"date-parts":[[2023,10,7]],"date-time":"2023-10-07T05:56:56Z","timestamp":1696658216000},"page":"1897-1910","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Dosing recommendation of nirmatrelvir\/ritonavir using an integrated population pharmacokinetic analysis"],"prefix":"10.1002","volume":"12","author":[{"given":"Phylinda L. S.","family":"Chan","sequence":"first","affiliation":[{"name":"Worldwide Research, Development and Medical Pfizer R&amp;D UK Ltd.  Sandwich, Kent UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ravi Shankar P.","family":"Singh","sequence":"additional","affiliation":[{"name":"Worldwide Research, Development and Medical Pfizer Inc.  Cambridge Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Donna S.","family":"Cox","sequence":"additional","affiliation":[{"name":"Worldwide Research, Development and Medical Pfizer Inc.  Collegeville Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haihong","family":"Shi","sequence":"additional","affiliation":[{"name":"Worldwide Research, Development and Medical Pfizer Inc.  Groton Connecticut USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bharat","family":"Damle","sequence":"additional","affiliation":[{"name":"Worldwide Research, Development and Medical Pfizer Inc.  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy","family":"Nicholas","sequence":"additional","affiliation":[{"name":"Worldwide Research, Development and Medical Pfizer Inc.  Groton Connecticut USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,10,6]]},"reference":[{"key":"e_1_2_11_2_1","unstructured":"World Health Organization.WHO coronavirus (COVID\u201019) dashboard.2023. Accessed July 11 2023.https:\/\/covid19.who.int\/"},{"key":"e_1_2_11_3_1","unstructured":"US Food and Drug Administration.Coronavirus (COVID\u201019) update: FDA authorizes first oral antiviral for treatment of COVID\u201019.2021. 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