{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,7]],"date-time":"2026-02-07T03:54:27Z","timestamp":1770436467518,"version":"3.49.0"},"reference-count":35,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2026,2,6]],"date-time":"2026-02-06T00:00:00Z","timestamp":1770336000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Charitable Trust Laboratory Medicine Research Foundation of Japan, JSPS KAKENHI","award":["23K09632"],"award-info":[{"award-number":["23K09632"]}]},{"name":"Morinomiyako Medical Research Foundation"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antibiotics"],"abstract":"<jats:p>Background\/Objectives: This study aimed to describe the population pharmacokinetics of cefazolin (CFZ) using unbound serum and periprostatic adipose tissue concentrations and to optimize dosing regimens for patients undergoing robotic-assisted radical prostatectomy (RARP). Methods: We investigated the population pharmacokinetics of CFZ using 295 unbound serum and 67 periprostatic adipose tissue samples from 67 individuals. CFZ concentrations were determined in all samples. A nonlinear mixed-effects model was developed. The pharmacodynamic target was defined as maintaining unbound trough and periprostatic adipose tissue concentrations exceeding the minimum inhibitory concentration (MIC) against methicillin-susceptible Staphylococcus aureus (MSSA) for over 90% of the dosing interval (MIC90; 0.5 mg\/L). Results: Systemic clearance of unbound CFZ was significantly associated with creatinine clearance (CLcr). In patients with normal renal function, simulations showed that a 1 g CFZ infusion over 15 min maintained unbound concentrations exceeding the MSSA MIC90 for &gt;90% of the 3 h interval after the initial dose. Notably, in patients with mild renal impairment (CLcr \u2264 80 mL\/min), a 5 h dosing interval also achieved a &gt;90% probability of maintaining the target CFZ concentration. Conclusions: The simulations demonstrated that the probability of target attainment of &gt;90% was maintained for up to 5 h in patients with mild renal impairment (CLcr \u2264 80 mL\/min). These findings provide a pharmacokinetic rationale suggesting that the standard additional dose may not be necessary for this subgroup; however, future clinical studies are needed to validate safety and efficacy.<\/jats:p>","DOI":"10.3390\/antibiotics15020181","type":"journal-article","created":{"date-parts":[[2026,2,6]],"date-time":"2026-02-06T13:33:50Z","timestamp":1770384830000},"page":"181","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Unbound and Periprostatic Adipose Tissue Cefazolin Pharmacokinetics in Robotic-Assisted Radical Prostatectomy"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4196-0756","authenticated-orcid":false,"given":"Toshiaki","family":"Komatsu","sequence":"first","affiliation":[{"name":"Department of Pharmacy, Kitasato University Hospital, Sagamihara 252-0375, Kanagawa, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuki","family":"Takahashi","sequence":"additional","affiliation":[{"name":"Pharmacy Practice and Science I, Research and Education Center for Clinical Pharmacy, Kitasato University School of Pharmacy, Sagamihara 252-0375, Kanagawa, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yoko","family":"Takayama","sequence":"additional","affiliation":[{"name":"Department of Infection Control and Infectious Diseases, Research and Development Center for New Medical Frontiers, Kitasato University School of Medicine, Sagamihara 252-0374, Kanagawa, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-8173-3318","authenticated-orcid":false,"given":"Yuto","family":"Akamada","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Kitasato University Hospital, Sagamihara 252-0375, Kanagawa, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1017-9799","authenticated-orcid":false,"given":"Masaomi","family":"Ikeda","sequence":"additional","affiliation":[{"name":"Department of Urology, Kitasato University School of Medicine, Sagamihara 252-0374, Kanagawa, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8962-2345","authenticated-orcid":false,"given":"Hideyasu","family":"Tsumura","sequence":"additional","affiliation":[{"name":"Department of Urology, Kitasato University School of Medicine, Sagamihara 252-0374, Kanagawa, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daisuke","family":"Ishii","sequence":"additional","affiliation":[{"name":"Department of Urology, Kitasato University School of Medicine, Sagamihara 252-0374, Kanagawa, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kazumasa","family":"Matsumoto","sequence":"additional","affiliation":[{"name":"Department of Urology, Kitasato University School of Medicine, Sagamihara 252-0374, Kanagawa, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masatsugu","family":"Iwamura","sequence":"additional","affiliation":[{"name":"Department of Urology, Kitasato University School of Medicine, Sagamihara 252-0374, Kanagawa, Japan"},{"name":"Department of Urology, Tomei Atsugi Hospital, Atsugi 243-0035, Kanagawa, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hirotsugu","family":"Okamoto","sequence":"additional","affiliation":[{"name":"Departments of Pharmacology and Anesthesiology, Kitasato University School of Medicine, Sagamihara 252-0374, Kanagawa, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hideaki","family":"Hanaki","sequence":"additional","affiliation":[{"name":"\u014cmura Satoshi Memorial Institute, Kitasato University, Minato-ku, Tokyo 108-8641, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katsuya","family":"Otori","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Kitasato University Hospital, Sagamihara 252-0375, Kanagawa, Japan"},{"name":"Pharmacy Practice and Science I, Research and Education Center for Clinical Pharmacy, Kitasato University School of Pharmacy, Sagamihara 252-0375, Kanagawa, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,2,6]]},"reference":[{"key":"ref_1","first-page":"229","article-title":"Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"74","author":"Bray","year":"2024","journal-title":"CA Cancer J. 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