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Pharmacokinetic determinants of cisplatin-induced subclinical kidney injury in oncology patients.
- Source :
-
European Journal of Clinical Pharmacology . Jan2019, Vol. 75 Issue 1, p51-57. 7p. 3 Charts, 1 Graph. - Publication Year :
- 2019
-
Abstract
- 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 1-h cisplatin infusion [30-75 mg/m2]. 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, days 3 and 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 2000 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. [ABSTRACT FROM AUTHOR]
- Subjects :
- *ACUTE kidney failure
*NEPHROTOXICOLOGY
*BIOMARKERS
*BLOOD proteins
*CALCIUM-binding proteins
*CARRIER proteins
*CISPLATIN
*STATISTICAL correlation
*CREATININE
*GLOBULINS
*GLOMERULAR filtration rate
*GLUTATHIONE
*GLYCOPROTEINS
*MASS spectrometry
*PLATINUM compounds
*REGRESSION analysis
*TUMORS
*ALBUMINS
*CYSTATINS
*TREFOIL factors
*URINE
*DISEASE risk factors
RISK factors
Subjects
Details
- Language :
- English
- ISSN :
- 00316970
- Volume :
- 75
- Issue :
- 1
- Database :
- Academic Search Index
- Journal :
- European Journal of Clinical Pharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 134058413
- Full Text :
- https://doi.org/10.1007/s00228-018-2552-z