Pharmacokinetic determinants of cisplatin-induced subclinical kidney injury in oncology patients
| Autor: | Lauren M. Aleksunes, Nickie Mercke, Brian Buckley, Cindy L. O'Bryant, Yichun Hu, Madeleine Gomez, Susan L. Hogan, Daniel W. Bowles, Melanie S. Joy, Mustafa E Ibrahim, Blessy George, Cara Chang, Xia Wen |
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| Rok vydání: | 2018 |
| Předmět: |
Male
medicine.medical_specialty Urinary system Urology Renal function Antineoplastic Agents 030226 pharmacology & pharmacy Article Nephrotoxicity 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Pharmacokinetics Neoplasms medicine Humans Pharmacology (medical) 030212 general & internal medicine Aged Pharmacology Creatinine biology Clusterin business.industry Acute kidney injury General Medicine Acute Kidney Injury Middle Aged medicine.disease chemistry Cystatin C biology.protein Regression Analysis Female Cisplatin business Biomarkers Glomerular Filtration Rate |
| Zdroj: | European Journal of Clinical Pharmacology. 75:51-57 |
| ISSN: | 1432-1041 0031-6970 |
| Popis: | PURPOSE: The ability to predict and detect clinical and subclinical nephrotoxicity early in the course of therapy has the potential to improve long-term outcomes in cancer patients receiving cisplatin chemotherapy. Pharmacokinetic parameters could serve as predictors of cisplatin-induced nephrotoxicity. METHODS: Participants [n=13] were treated with a one-hour cisplatin infusion [30–75 mg/m(2)]. Blood was collected pre-dose and up to 6 h post-dose. Urinary biomarkers [KIM-1, calbindin, clusterin, GST-pi, β2M, albumin, NGAL, osteopontin, clusterin, MCP-1, cystatin C and TFF3] were measured at baseline, day 3 and day 10. Total and unbound platinum concentrations were measured using ICP/MS. Noncompartmental analysis was performed and correlation and regression analyses evaluated the relationships between platinum pharmacokinetics and nephrotoxicity. RESULTS: Peak platinum urinary concentrations correlated with urinary levels of KIM-1, calbindin, clusterin, GST-pi, β2M, albumin, NGAL, osteopontin, clusterin, cystatin C and TFF3 at day 10. Unbound platinum plasma concentrations at 2 h also correlated with urinary clusterin, β2M, cystatin C, NGAL, osteopontin, and TFF3 at day 3. Regression analyses suggested 2 h total plasma platinum concentrations greater than 2,000 ng/ml and peak urinary platinum concentrations above 24,000 ng/ml may serve as potential approximations for elevated risk of nephrotoxicity. Platinum area under the plasma concentration time curve was associated with serum creatinine and estimated glomerular filtration rate. CONCLUSIONS: Peak plasma and urinary platinum concentrations and pharmacokinetic parameters were associated with risk of subclinical cisplatin-induced kidney injury as assessed using novel urinary biomarkers. Future studies will examine these relationships in larger clinical populations of cisplatin-induced acute kidney injury. |
| Databáze: | OpenAIRE |
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