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Population Pharmacokinetic Model of Platinum Disposition in Cancer Patients Receiving Cisplatin and Randomized to 5‐HT3 Antagonist Antiemetic Drugs.

Λεπτομέρειες βιβλιογραφικής εγγραφής
Τίτλος: Population Pharmacokinetic Model of Platinum Disposition in Cancer Patients Receiving Cisplatin and Randomized to 5‐HT3 Antagonist Antiemetic Drugs.
Συγγραφείς: Thompson, Lauren E., Ghimire, Avisek, Wen, Xia, Kim, Christine, Doherty, Cathleen L., Buckley, Brian T., Bowles, Daniel W., O'Bryant, Cindy L., Jaimes, Edgar A., Aleksunes, Lauren M., Joy, Melanie S.
Πηγή: Journal of Clinical Pharmacology; Jun2025, Vol. 65 Issue 6, p763-778, 16p
Θεματικοί όροι: Biological models, Pearson correlation (Statistics), Cisplatin, Research funding, Blood chemical analysis, T-test (Statistics), Antiemetics, Statistical sampling, Kruskal-Wallis Test, Cancer patients, Randomized controlled trials, Descriptive statistics, Mann Whitney U Test, Cancer chemotherapy, Longitudinal method, Mass spectrometry, One-way analysis of variance, Comparative studies, Platinum, Serotonin antagonists, Regression analysis
Γεωγραφικοί όροι: United States
Περίληψη: Cisplatin is a platinum‐based chemotherapeutic drug used to treat many types of cancer. The aim of this study was to develop a population pharmacokinetic model that incorporates plasma unbound and bound platinum levels. Cancer patients undergoing their first or second cycle of cisplatin‐containing chemotherapy (n = 33) were prospectively randomized to receive a 5‐hydroxytryptamine (5‐HT3) antagonist (5‐HT3A) antiemetic (ondansetron, granisetron, or palonosetron) followed by blood collection over 10 days. Total and unbound platinum levels were quantified using inductively coupled plasma mass spectrometry. Plasma concentrations of bound and unbound platinum were used to develop a nonlinear mixed‐effect pharmacokinetic model in Phoenix NLME (v8.3, Certara Inc.). A stepwise search was used to screen covariates that influenced pharmacokinetic parameters. A compartment for bound platinum was added to a two‐compartment unbound platinum model to create a combined platinum model. The volume of the central compartment for unbound platinum (V1_u) was significantly impacted by previous cisplatin exposure and the intercompartmental clearance of unbound platinum (CL2_u) was significantly influenced by concomitant lorazepam use. The models also suggested ondansetron‐ and granisetron‐treated subjects had a 331% and 114% increase, respectively, in circulating exposures to unbound platinum than palonosetron‐treated subjects. The results suggest platinum pharmacokinetics are altered by concomitant 5‐HT3A antiemetic use, concomitant lorazepam use, and previous exposure to cisplatin. Ondansetron and granisetron co‐treatment increased unbound platinum exposure compared to palonosetron co‐treatment, suggesting that palonosetron may be a preferred 5‐HT3A to reduce the risk of cisplatin‐induced kidney injury. [ABSTRACT FROM AUTHOR]
Copyright of Journal of Clinical Pharmacology is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
Βάση Δεδομένων: Complementary Index
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PubType: Academic Journal
PubTypeId: academicJournal
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  Data: Journal of Clinical Pharmacology; Jun2025, Vol. 65 Issue 6, p763-778, 16p
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  Data: Cisplatin is a platinum‐based chemotherapeutic drug used to treat many types of cancer. The aim of this study was to develop a population pharmacokinetic model that incorporates plasma unbound and bound platinum levels. Cancer patients undergoing their first or second cycle of cisplatin‐containing chemotherapy (n = 33) were prospectively randomized to receive a 5‐hydroxytryptamine (5‐HT3) antagonist (5‐HT3A) antiemetic (ondansetron, granisetron, or palonosetron) followed by blood collection over 10 days. Total and unbound platinum levels were quantified using inductively coupled plasma mass spectrometry. Plasma concentrations of bound and unbound platinum were used to develop a nonlinear mixed‐effect pharmacokinetic model in Phoenix NLME (v8.3, Certara Inc.). A stepwise search was used to screen covariates that influenced pharmacokinetic parameters. A compartment for bound platinum was added to a two‐compartment unbound platinum model to create a combined platinum model. The volume of the central compartment for unbound platinum (V1_u) was significantly impacted by previous cisplatin exposure and the intercompartmental clearance of unbound platinum (CL2_u) was significantly influenced by concomitant lorazepam use. The models also suggested ondansetron‐ and granisetron‐treated subjects had a 331% and 114% increase, respectively, in circulating exposures to unbound platinum than palonosetron‐treated subjects. The results suggest platinum pharmacokinetics are altered by concomitant 5‐HT3A antiemetic use, concomitant lorazepam use, and previous exposure to cisplatin. Ondansetron and granisetron co‐treatment increased unbound platinum exposure compared to palonosetron co‐treatment, suggesting that palonosetron may be a preferred 5‐HT3A to reduce the risk of cisplatin‐induced kidney injury. [ABSTRACT FROM AUTHOR]
– Name: Abstract
  Label:
  Group: Ab
  Data: <i>Copyright of Journal of Clinical Pharmacology is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.)
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RecordInfo BibRecord:
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      – Type: doi
        Value: 10.1002/jcph.6177
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      – Code: eng
        Text: English
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        PageCount: 16
        StartPage: 763
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      – SubjectFull: Cisplatin
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      – SubjectFull: Blood chemical analysis
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      – SubjectFull: T-test (Statistics)
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      – SubjectFull: Antiemetics
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      – SubjectFull: Statistical sampling
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      – SubjectFull: Kruskal-Wallis Test
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      – SubjectFull: Cancer patients
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      – SubjectFull: Mann Whitney U Test
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      – SubjectFull: Regression analysis
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      – TitleFull: Population Pharmacokinetic Model of Platinum Disposition in Cancer Patients Receiving Cisplatin and Randomized to 5‐HT3 Antagonist Antiemetic Drugs.
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              Text: Jun2025
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