In vivo evaluation of drug dialyzability in a rat model of hemodialysis
It is important to calculate the drug removal by hemodialysis (HD) for drug dosing regimens in HD patients. However, there are limited and inconsistent information about the dialyzability of drugs by HD. Therefore, the aim of our study is to evaluate drug removal by utilizing a rat model of HD (HD r...
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| creator | Fukunaga, Masaki Kadowaki, Daisuke Mori, Mika Hagiwara, Satomi Narita, Yuki Saruwatari, Junji Tanaka, Ryota Watanabe, Hiroshi Yamasaki, Keishi Taguchi, Kazuaki Ito, Hiroki Maruyama, Toru Otagiri, Masaki Hirata, Sumio |
| description | It is important to calculate the drug removal by hemodialysis (HD) for drug dosing regimens in HD patients. However, there are limited and inconsistent information about the dialyzability of drugs by HD. Therefore, the aim of our study is to evaluate drug removal by utilizing a rat model of HD (HD rat) and to extrapolate this result to the drug removal rate in HD patients. HD rats received bilateral nephrectomy and HD for 2 h. The dialysis removal of 6 drugs was evaluated in HD rats. Dialysis efficiency, plasma protein binding rate (PBR) and distribution volume (Vd) of drugs were also measured. Furthermore, we examined the correlation between the dialyzability of drug in HD rats and humans and constructed the prediction formula of the drug dialyzability in HD patients. The clearance of urea and creatinine and normalized dialysis dose in HD rats were 0.83 ± 0.07 mL/min, 0.70 ± 0.08 mL/min, and 0.13 ± 0.06, respectively. The drug dialyzability in HD rats was similar to reported clinical data except for doripenem. A higher correlation was observed between drug dialyzability in reported clinical data and HD rats which were adjusted for PBR (r.sup.2 = 0.936; p < 0.001) compared to unadjusted (r.sup.2 = 0.812; p = 0.009). Therefore, we constructed the prediction formula of the drug dialyzability in HD patients by utilizing the HD rat model and PBR. This study is useful for evaluating the dialyzability of high-risk drugs in a clinical setting and might provide appropriate preclinical dialyzability data for new drug. |
| doi_str_mv | 10.1371/journal.pone.0233925 |
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However, there are limited and inconsistent information about the dialyzability of drugs by HD. Therefore, the aim of our study is to evaluate drug removal by utilizing a rat model of HD (HD rat) and to extrapolate this result to the drug removal rate in HD patients. HD rats received bilateral nephrectomy and HD for 2 h. The dialysis removal of 6 drugs was evaluated in HD rats. Dialysis efficiency, plasma protein binding rate (PBR) and distribution volume (Vd) of drugs were also measured. Furthermore, we examined the correlation between the dialyzability of drug in HD rats and humans and constructed the prediction formula of the drug dialyzability in HD patients. The clearance of urea and creatinine and normalized dialysis dose in HD rats were 0.83 ± 0.07 mL/min, 0.70 ± 0.08 mL/min, and 0.13 ± 0.06, respectively. The drug dialyzability in HD rats was similar to reported clinical data except for doripenem. A higher correlation was observed between drug dialyzability in reported clinical data and HD rats which were adjusted for PBR (r.sup.2 = 0.936; p < 0.001) compared to unadjusted (r.sup.2 = 0.812; p = 0.009). Therefore, we constructed the prediction formula of the drug dialyzability in HD patients by utilizing the HD rat model and PBR. This study is useful for evaluating the dialyzability of high-risk drugs in a clinical setting and might provide appropriate preclinical dialyzability data for new drug.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0233925</identifier><identifier>PMID: 32530952</identifier><language>eng</language><publisher>San Francisco: Public Library of Science</publisher><subject>Analysis ; Animals ; Biology and Life Sciences ; Catheters ; Correlation ; Correlation analysis ; Creatinine ; Dialysate ; Dialysis ; Dialyzers ; Dosage ; Drug development ; Drug dosages ; Drug interactions ; Drug therapy ; Drugs ; Engineering and Technology ; Evaluation ; Hemodialysis ; Hemodialysis patients ; Laboratories ; Medicine and Health Sciences ; Nephrectomy ; Pharmaceutical sciences ; Pharmacy ; Physical Sciences ; Physiology ; R&D ; Research & development ; Research and Analysis Methods ; Sodium ; Urea ; Veins & arteries</subject><ispartof>PloS one, 2020-06, Vol.15 (6), p.e0233925-e0233925</ispartof><rights>COPYRIGHT 2020 Public Library of Science</rights><rights>2020 Fukunaga et al. 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However, there are limited and inconsistent information about the dialyzability of drugs by HD. Therefore, the aim of our study is to evaluate drug removal by utilizing a rat model of HD (HD rat) and to extrapolate this result to the drug removal rate in HD patients. HD rats received bilateral nephrectomy and HD for 2 h. The dialysis removal of 6 drugs was evaluated in HD rats. Dialysis efficiency, plasma protein binding rate (PBR) and distribution volume (Vd) of drugs were also measured. Furthermore, we examined the correlation between the dialyzability of drug in HD rats and humans and constructed the prediction formula of the drug dialyzability in HD patients. The clearance of urea and creatinine and normalized dialysis dose in HD rats were 0.83 ± 0.07 mL/min, 0.70 ± 0.08 mL/min, and 0.13 ± 0.06, respectively. The drug dialyzability in HD rats was similar to reported clinical data except for doripenem. A higher correlation was observed between drug dialyzability in reported clinical data and HD rats which were adjusted for PBR (r.sup.2 = 0.936; p < 0.001) compared to unadjusted (r.sup.2 = 0.812; p = 0.009). Therefore, we constructed the prediction formula of the drug dialyzability in HD patients by utilizing the HD rat model and PBR. This study is useful for evaluating the dialyzability of high-risk drugs in a clinical setting and might provide appropriate preclinical dialyzability data for new drug.</abstract><cop>San Francisco</cop><pub>Public Library of Science</pub><pmid>32530952</pmid><doi>10.1371/journal.pone.0233925</doi><tpages>e0233925</tpages><orcidid>https://orcid.org/0000-0003-3821-5966</orcidid><orcidid>https://orcid.org/0000-0003-1584-249X</orcidid><orcidid>https://orcid.org/0000-0002-3064-1963</orcidid><oa>free_for_read</oa></addata></record> |
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| source | DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central; Free Full-Text Journals in Chemistry; Public Library of Science (PLoS) |
| subjects | Analysis Animals Biology and Life Sciences Catheters Correlation Correlation analysis Creatinine Dialysate Dialysis Dialyzers Dosage Drug development Drug dosages Drug interactions Drug therapy Drugs Engineering and Technology Evaluation Hemodialysis Hemodialysis patients Laboratories Medicine and Health Sciences Nephrectomy Pharmaceutical sciences Pharmacy Physical Sciences Physiology R&D Research & development Research and Analysis Methods Sodium Urea Veins & arteries |
| title | In vivo evaluation of drug dialyzability in a rat model of hemodialysis |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-30T21%3A43%3A14IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=In%20vivo%20evaluation%20of%20drug%20dialyzability%20in%20a%20rat%20model%20of%20hemodialysis&rft.jtitle=PloS%20one&rft.au=Fukunaga,%20Masaki&rft.date=2020-06-12&rft.volume=15&rft.issue=6&rft.spage=e0233925&rft.epage=e0233925&rft.pages=e0233925-e0233925&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0233925&rft_dat=%3Cgale_plos_%3EA626469863%3C/gale_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2412532996&rft_id=info:pmid/32530952&rft_galeid=A626469863&rft_doaj_id=oai_doaj_org_article_0411000611ae4ea4a8b5c0f1f817187d&rfr_iscdi=true |