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Relevance of plasma lenvatinib concentrations and endogenous urinary cytochrome P450 3A activity biomarkers in clinical practice.

التفاصيل البيبلوغرافية
العنوان: Relevance of plasma lenvatinib concentrations and endogenous urinary cytochrome P450 3A activity biomarkers in clinical practice.
المؤلفون: Kumondai M; Department of Pharmaceutical Sciences, Tohoku University Hospital, Sendai, Japan., Ogawa R; Department of Pharmaceutical Sciences, Tohoku University Hospital, Sendai, Japan., Hayashi N; Faculty of Pharmaceutical Sciences, Tohoku University, Sendai, Japan., Ishida Y; Department of Pharmaceutical Sciences, Tohoku University Hospital, Sendai, Japan., Oshikiri H; Department of Pharmaceutical Sciences, Tohoku University Hospital, Sendai, Japan., Sato Y; Department of Pharmaceutical Sciences, Tohoku University Hospital, Sendai, Japan., Kikuchi M; Department of Pharmaceutical Sciences, Tohoku University Hospital, Sendai, Japan.; Faculty of Pharmaceutical Sciences, Tohoku University, Sendai, Japan., Sato Y; Department of Pharmaceutical Sciences, Tohoku University Hospital, Sendai, Japan., Sato T; Department of Pharmaceutical Sciences, Tohoku University Hospital, Sendai, Japan., Maekawa M; Department of Pharmaceutical Sciences, Tohoku University Hospital, Sendai, Japan.; Faculty of Pharmaceutical Sciences, Tohoku University, Sendai, Japan., Mano N; Department of Pharmaceutical Sciences, Tohoku University Hospital, Sendai, Japan.; Faculty of Pharmaceutical Sciences, Tohoku University, Sendai, Japan.
المصدر: Pharmacology research & perspectives [Pharmacol Res Perspect] 2024 Aug; Vol. 12 (4), pp. e1241.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: John Wiley & Sons Ltd, British Pharmacological Society and American Society for Pharmacology and Experimental Therapeutics Country of Publication: United States NLM ID: 101626369 Publication Model: Print Cited Medium: Internet ISSN: 2052-1707 (Electronic) Linking ISSN: 20521707 NLM ISO Abbreviation: Pharmacol Res Perspect Subsets: MEDLINE
أسماء مطبوعة: Original Publication: [Hoboken, NJ] : John Wiley & Sons Ltd, British Pharmacological Society and American Society for Pharmacology and Experimental Therapeutics, [2013]-
مواضيع طبية MeSH: Phenylurea Compounds*/urine , Phenylurea Compounds*/pharmacokinetics , Phenylurea Compounds*/blood , Phenylurea Compounds*/therapeutic use , Phenylurea Compounds*/administration & dosage , Quinolines*/urine , Quinolines*/therapeutic use , Quinolines*/blood , Quinolines*/administration & dosage , Quinolines*/pharmacokinetics , Cytochrome P-450 CYP3A*/metabolism , Biomarkers*/urine , Biomarkers*/blood , Drug Monitoring*/methods, Humans ; Female ; Aged ; Middle Aged ; Male ; Adult ; Aged, 80 and over ; Antineoplastic Agents/urine ; Antineoplastic Agents/therapeutic use ; Antineoplastic Agents/blood ; Antineoplastic Agents/pharmacokinetics ; Protein Kinase Inhibitors/urine ; Protein Kinase Inhibitors/blood ; Protein Kinase Inhibitors/therapeutic use ; Protein Kinase Inhibitors/pharmacokinetics ; Protein Kinase Inhibitors/administration & dosage ; Neoplasms/drug therapy ; Neoplasms/blood ; Neoplasms/urine ; Tandem Mass Spectrometry/methods ; Endometrial Neoplasms/drug therapy ; Endometrial Neoplasms/urine ; Endometrial Neoplasms/blood ; Carcinoma, Hepatocellular/drug therapy ; Carcinoma, Hepatocellular/blood ; Carcinoma, Hepatocellular/urine ; Chromatography, Liquid/methods ; Thyroid Neoplasms/drug therapy ; Thyroid Neoplasms/urine ; Thyroid Neoplasms/blood ; Liver Neoplasms/drug therapy ; Liver Neoplasms/blood ; Liver Neoplasms/urine ; Carcinoma, Renal Cell/drug therapy ; Carcinoma, Renal Cell/urine ; Carcinoma, Renal Cell/blood ; Hydrocortisone/analogs & derivatives
مستخلص: Lenvatinib (LEN), a multitarget tyrosine kinase inhibitor used in various cancer treatments, is mainly metabolized by cytochrome P450 3A (CYP3A) enzymes. The importance of therapeutic drug monitoring (TDM) in patients administered LEN has been proposed. Although some biomarkers of endogenous CYP3A activity have been reported, their utility in dosage adjustments has not been well evaluated. This study investigated the correlation between plasma LEN concentrations and endogenous urinary CYP3A biomarkers in clinical practice. Concentrations of plasma LEN (N = 225) and CYP3A biomarkers (cortisol, 6β-hydroxycortisol, deoxycholic acid, and 1β-hydroxydeoxycholic acid) in urine (N = 214) from 20 patients (hepatocellular carcinoma, N = 6; thyroid cancer, N = 3; endometrial cancer, N = 8; and renal cell carcinoma, N = 3) collected for consultation for up to 1 year were evaluated using liquid chromatography-tandem mass spectrometry. Moreover, plasma trough LEN concentrations were predicted using a three-compartment model with linear elimination for outpatients administered LEN before sample collection. Moderate correlations were observed between the quantified actual concentrations and the predicted trough concentrations of LEN, whereas there was no correlation with endogenous urinary CYP3A biomarkers. The utility of endogenous urinary CYP3A biomarkers could not be determined. However, TDM for outpatients administered orally available medicines may be predicted using a nonlinear mixed effect model (NONMEM). This study investigated the utility of endogenous urinary CYP3A biomarkers for personalized medicine and NONMEM for predicting plasma trough drug concentrations. These findings will provide important information for further clinical investigation and detailed TDM.
(© 2024 The Author(s). Pharmacology Research & Perspectives published by British Pharmacological Society and American Society for Pharmacology and Experimental Therapeutics and John Wiley & Sons Ltd.)
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معلومات مُعتمدة: 22 K15333 Japan Society for the Promotion of Science
فهرسة مساهمة: Keywords: biomarkers; cytochrome P450 3A; lenvatinib; therapeutic drug monitoring
المشرفين على المادة: EE083865G2 (lenvatinib)
0 (Phenylurea Compounds)
0 (Quinolines)
EC 1.14.14.1 (Cytochrome P-450 CYP3A)
0 (Biomarkers)
0 (Antineoplastic Agents)
0 (Protein Kinase Inhibitors)
53-35-0 (6 beta-hydroxycortisol)
EC 1.14.14.1 (CYP3A protein, human)
WI4X0X7BPJ (Hydrocortisone)
تواريخ الأحداث: Date Created: 20240712 Date Completed: 20240712 Latest Revision: 20240714
رمز التحديث: 20240714
مُعرف محوري في PubMed: PMC11239757
DOI: 10.1002/prp2.1241
PMID: 38992911
قاعدة البيانات: MEDLINE
الوصف
تدمد:2052-1707
DOI:10.1002/prp2.1241