{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T02:24:46Z","timestamp":1789698286237,"version":"4.0.1"},"reference-count":31,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,4,7]],"date-time":"2026-04-07T00:00:00Z","timestamp":1775520000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003197","name":"Agenzia Italiana Del Farmaco, Ministero Della Salute","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003197","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Women with Parkinson\u2019s Disease (PD) have higher plasma exposure to levodopa and are particularly prone to developing complications during chronic levodopa therapy. However, there are no longitudinal studies focusing on differences in levodopa pharmacokinetics and their correlation with clinical outcomes. This multicenter longitudinal study aimed to investigate sex-related differences in levodopa pharmacokinetics in levodopa-na\u00efve PD patients, and to evaluate relationships with levodopa-related complications.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>After a single dose of levodopa\/DOPA-decarboxylase inhibitor, blood samples were collected at baseline and at two-year follow-up to measure pharmacokinetic parameters using UHPLC-MS. Clinical assessment included wearing-off Questionnaire and MDS-UPDRS scale. Multiple linear regression analyses were performed to identify predictors of pharmacokinetic parameters and levodopa-related complications.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results and Discussion<\/jats:title>\n                    <jats:p>The study population consisted of 28 PD patients (18 men, 10 women) followed for 2 years from the start of levodopa therapy. No differences were found between the sexes in clinical characteristics, daily levodopa-dosage, and use of other antiparkinsonian drugs. AUC and Cmax were higher in females than in males (p &amp;lt; 0.001), and sex influenced both of these parameters regardless of whether pharmacokinetic analysis was performed at baseline or at follow-up. Female sex was the best predictor of AUC and Cmax. DYS was found in 20% of females but in no males, and 90% of females showed wearing-off compared to 50% of males (p = 0.022). In females but not in males, the presence of wearing -off was correlated with AUC and Cmax at baseline and after 2 years of treatment. Compared to men, women with PD showed higher plasma levodopa levels since the initial administration and after chronic treatment. Measuring exposure to levodopa may be useful for optimising levodopa dosage since the start of treatment, thus preventing levodopa-related complications.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fphar.2026.1748932","type":"journal-article","created":{"date-parts":[[2026,4,7]],"date-time":"2026-04-07T05:35:04Z","timestamp":1775540104000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Sex differences in levodopa pharmacokinetics in early Parkinson\u2019s disease: implications on levodopa-related complications"],"prefix":"10.3389","volume":"17","author":[{"given":"Valeria","family":"Conti","sequence":"first","affiliation":[{"name":"Department of Medicine, Surgery, and Dentistry, Scuola Medica Salernitana, University of Salerno","place":["Baronissi, Italy"]},{"name":"Clinical Pharmacology Unit, San Giovanni di Dio e Ruggi d\u2019Aragona University Hospital","place":["Salerno, 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delle Scienze Neurologiche di Bologna\u201d, UOC Neurological Clinic, Bellaria Hospital","place":["Bologna, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Calogero Edoardo","family":"Cicero","sequence":"additional","affiliation":[{"name":"Neurologic Unit, AOU \u201cPoliclinico-San Marco\u201d, Department of Medical, Surgical Sciences and Advanced Technologies, GF Ingrassia, University of Catania","place":["Catania, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandra","family":"Nicoletti","sequence":"additional","affiliation":[{"name":"Neurologic Unit, AOU \u201cPoliclinico-San Marco\u201d, Department of Medical, Surgical Sciences and Advanced Technologies, GF Ingrassia, University of Catania","place":["Catania, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Soricelli","sequence":"additional","affiliation":[{"name":"IRCCS SYNLAB SDN","place":["Naples, 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