{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,18]],"date-time":"2026-05-18T03:08:19Z","timestamp":1779073699268,"version":"3.51.4"},"reference-count":31,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2026,4,21]],"date-time":"2026-04-21T00:00:00Z","timestamp":1776729600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,4,21]],"date-time":"2026-04-21T00:00:00Z","timestamp":1776729600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100004319","name":"Pfizer","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004319","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Translational Sci"],"published-print":{"date-parts":[[2026,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>In accordance with the Centers for Disease Control and Prevention recommendations, pregnant women and those with a recent pregnancy (i.e., lactating) are considered at high risk of developing severe COVID\u201019 and qualify for treatment with nirmatrelvir\/ritonavir. However, clinical data are lacking in this population because breastfeeding women were excluded from the nirmatrelvir\/ritonavir clinical development program and pivotal Phase 2\/3 studies. We report findings from a prospective Phase 1 trial (NCT05441215) designed and conducted in accordance with the US Food and Drug Administration guidance on clinical lactation studies that evaluated the pharmacokinetics and safety of multiple oral doses of nirmatrelvir\/ritonavir in healthy lactating women using paired breast milk and maternal plasma data. Eight participants were enrolled and completed the study. After administration of nirmatrelvir\/ritonavir 300\u2009mg\/100\u2009mg to steady\u2010state, the concentrations of both nirmatrelvir and ritonavir in breast milk were consistently lower than maternal plasma. Based on standard infant breast milk consumption (150\u2009mL\/kg\/day), the mean absolute daily doses of nirmatrelvir and ritonavir that an infant would receive were 0.1595 and 0.0057\u2009mg\/kg\/day, respectively, representing 1.8% and 0.19% of the bodyweight\u2010normalized maternal dose. All treatment\u2010emergent adverse events were mild to moderate in severity. No deaths, serious or severe adverse events, dose reductions, interruptions, or discontinuations were reported. In conclusion, nirmatrelvir\/ritonavir 300\u2009mg\/100\u2009mg was safe and well tolerated in healthy lactating women, with infant exposure considered to be low and well within the acceptability criteria of &lt;\u200910% of the body weight\u2010normalized maternal dose.<\/jats:p>","DOI":"10.1111\/cts.70552","type":"journal-article","created":{"date-parts":[[2026,4,21]],"date-time":"2026-04-21T13:49:13Z","timestamp":1776779353000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["A Phase 1 Multiple\u2010Dose, Open\u2010Label, Pharmacokinetic Study of Nirmatrelvir\/Ritonavir in Healthy Lactating Women"],"prefix":"10.1111","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4679-4638","authenticated-orcid":false,"given":"Jacqueline","family":"Gerhart","sequence":"first","affiliation":[{"name":"Pfizer Research and Development Pfizer Inc  Collegeville Pennsylvania USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-4343-086X","authenticated-orcid":false,"given":"Narayan","family":"Cheruvu","sequence":"additional","affiliation":[{"name":"Pfizer Research and Development Pfizer Inc  Collegeville Pennsylvania USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kathleen","family":"Pelletier","sequence":"additional","affiliation":[{"name":"Pfizer Research and Development Pfizer Inc  Groton Connecticut USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-2043-851X","authenticated-orcid":false,"given":"Kyle","family":"Matschke","sequence":"additional","affiliation":[{"name":"Pfizer Research and Development Pfizer Inc  Collegeville Pennsylvania USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Haihong","family":"Shi","sequence":"additional","affiliation":[{"name":"Pfizer Research and Development Pfizer Inc  Groton Connecticut USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3058-1996","authenticated-orcid":false,"given":"Josu\u00e9 Kunjom","family":"Mfopou","sequence":"additional","affiliation":[{"name":"Pfizer Clinical Research Unit Pfizer S.A.\/N.V.  Brussels Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4810-8558","authenticated-orcid":false,"given":"Jennifer","family":"Hammond","sequence":"additional","affiliation":[{"name":"Pfizer Research and Development Pfizer Inc  Collegeville Pennsylvania USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6298-8219","authenticated-orcid":false,"given":"Ravi Shankar P.","family":"Singh","sequence":"additional","affiliation":[{"name":"Pfizer Research and Development Pfizer Inc  Cambridge Massachusetts USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2026,4,21]]},"reference":[{"key":"e_1_2_10_2_1","unstructured":"United States Department of AgricultureandDepartment of Health and Human Services Dietary Guidelines for Americans 2020\u20132025 9th ed. accessed November 20 2024 https:\/\/www.cdc.gov\/breastfeeding\u2010data\/media\/pdfs\/2024\/05\/Dietary_Guidelines_for_Americans_2020\u20102025.pdf#page=65."},{"key":"e_1_2_10_3_1","unstructured":"World Health Organization \u201cBreastfeeding. Recommendations \u201daccessed November 20 2024 https:\/\/www.who.int\/health\u2010topics\/breastfeeding#tab=tab_2."},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1542\/peds.2022-057988"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/bcp.13438"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/s44294-025-00064-0"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0169-409X(03)00032-2"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpt.3059"},{"key":"e_1_2_10_9_1","unstructured":"US Food and Drug Administration \u201cClinical Lactation Studies: Considerations for Study Design Guidance for Industry \u201daccessed October 30 2024 https:\/\/www.fda.gov\/regulatory\u2010information\/search\u2010fda\u2010guidance\u2010documents\/clinical\u2010lactation\u2010studies\u2010considerations\u2010study\u2010design."},{"key":"e_1_2_10_10_1","unstructured":"International Council For Harmonisation of Technical Requirements for Pharmaceuticals for Human Use \u201cE21: Inclusion of Pregnant and Breast\u2010Feeding Individuals in Clinical Trials: Final Concept Paper \u201daccessed June 23 2025 https:\/\/database.ich.org\/sites\/default\/files\/ICH_E21_Final_Concept_Paper_2023_1106_MCApproved.pdf."},{"key":"e_1_2_10_11_1","unstructured":"Centers for Disease Control and Prevention \u201cCOVID\u201019 and Breastfeeding \u201daccessed April 1 2025 https:\/\/www.cdc.gov\/breastfeeding\u2010special\u2010circumstances\/hcp\/illnesses\u2010conditions\/covid\u201019.html#cdc_generic_section_1\u2010about\u2010covid\u201019."},{"key":"e_1_2_10_12_1","unstructured":"Centers for Disease Control and Prevention \u201cUnderlying Conditions and the Higher Risk for Severe COVID\u201019 \u201daccessed November 25 2024 https:\/\/www.cdc.gov\/covid\/hcp\/clinical\u2010care\/underlying\u2010conditions.html."},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamapediatrics.2021.1050"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12884-024-06767-7"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1111\/aogs.14329"},{"key":"e_1_2_10_16_1","unstructured":"\u201cPaxlovid (Nirmatrelvir Tablets; Ritonavir Tablets). 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