{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,5,13]],"date-time":"2025-05-13T14:33:27Z","timestamp":1747146807890,"version":"3.40.5"},"reference-count":40,"publisher":"Wiley","issue":"4-5","license":[{"start":{"date-parts":[[2020,4,12]],"date-time":"2020-04-12T00:00:00Z","timestamp":1586649600000},"content-version":"vor","delay-in-days":11,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Biopharm &amp; Drug Disp"],"published-print":{"date-parts":[[2020,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>This study aimed to investigate the applicability of the \u00d8ie\u2010Tozer model to predict human distribution volume (Vd) in the central compartment (V<jats:sub>1<\/jats:sub>), Vd at steady state (Vd<jats:sub>ss<\/jats:sub>), and Vd at beta phase (Vd<jats:sub>\u03b2<\/jats:sub>) based on animal Vd. Twenty compounds that have a human V<jats:sub>1<\/jats:sub>\/Vd<jats:sub>ss<\/jats:sub> of 0.053\u20130.66 were selected from the literature. After intravenous administration of the compounds at 0.1 mg\/kg to rats, dogs, and monkeys, plasma concentrations were determined, and pharmacokinetic parameters were obtained by one\/two\u2010compartmental analyses. The human V<jats:sub>1<\/jats:sub>, Vd<jats:sub>ss<\/jats:sub>, and Vd<jats:sub>\u03b2<\/jats:sub> were predicted from animal Vd using the \u00d8ie\u2010Tozer model, and the predictability was compared with that using proportionality and simple allometry. The \u00d8ie\u2010Tozer model was the most reliable method for the overall prediction of Vd and applicable for accurately predicting human V<jats:sub>1<\/jats:sub>, Vd<jats:sub>ss<\/jats:sub>, and Vd<jats:sub>\u03b2<\/jats:sub> (89%, 85%, and 68% of the compounds within a 3\u2010fold error, respectively) when data of monkey for V<jats:sub>1<\/jats:sub> and data of three animal species for Vd<jats:sub>ss<\/jats:sub> and Vd<jats:sub>\u03b2<\/jats:sub> were used. Additionally, the predicted human Vd with the two\u2010compartment model was applicable for predicting pharmacokinetic profiles\/parameters in humans after intravenous administration of 18 compounds [except for valproic acid (monophasic elimination profile) and chlorpromazine (deviation: Vd<jats:sub>ss<\/jats:sub> &lt; V<jats:sub>1<\/jats:sub>)]. The prediction was more accurate than that using the predicted Vd<jats:sub>ss<\/jats:sub> with the one\u2010compartment model (e.g., underestimation of maximum plasma concentrations: 2 vs 8 compounds within a 3\u2010fold error, respectively). In summary, the \u00d8ie\u2010Tozer model was applicable for predicting human V<jats:sub>1<\/jats:sub>, Vd<jats:sub>ss<\/jats:sub>, and Vd<jats:sub>\u03b2<\/jats:sub>, and their predicted Vd with the two\u2010compartment model can lead to accurate pharmacokinetic prediction of compounds that show biphasic elimination.<\/jats:p>","DOI":"10.1002\/bdd.2224","type":"journal-article","created":{"date-parts":[[2020,3,18]],"date-time":"2020-03-18T21:14:26Z","timestamp":1584566066000},"page":"151-165","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Applicability of the \u00d8ie\u2010Tozer model to predict three types of distribution volume (Vd) in humans: Vd in central compartment, Vd at steady state, and Vd at beta phase"],"prefix":"10.1002","volume":"41","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9528-9913","authenticated-orcid":false,"given":"Masahiro","family":"Yahata","sequence":"first","affiliation":[{"name":"Preclinical Research Unit Sumitomo Dainippon Pharma Co., Ltd  Osaka Japan"},{"name":"Laboratory of Molecular Life Sciences, Graduate School of Pharmaceutical Sciences Kyushu University  Fukuoka Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuji","family":"Ishii","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Life Sciences, Graduate School of Pharmaceutical Sciences Kyushu University  Fukuoka Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tetsuya","family":"Nakagawa","sequence":"additional","affiliation":[{"name":"Preclinical Research Unit Sumitomo Dainippon Pharma Co., Ltd  Osaka Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takao","family":"Watanabe","sequence":"additional","affiliation":[{"name":"Preclinical Research Unit Sumitomo Dainippon Pharma Co., Ltd  Osaka Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Izuru","family":"Miyawaki","sequence":"additional","affiliation":[{"name":"Preclinical Research Unit Sumitomo Dainippon Pharma Co., Ltd  Osaka Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2020,4,12]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2125.1986.tb02935.x"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2125.1999.00936.x"},{"issue":"1","key":"e_1_2_7_4_1","first-page":"91","article-title":"Pharmacokinetics, absolute bioavailability, and disposition of [14C]nefazodone in humans","volume":"24","author":"Barbhaiya R. 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