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Intraperitoneal clearance as a potential biomarker of cisplatin after intraperitoneal perioperative chemotherapy: a population pharmacokinetic study
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Intraperitoneal clearance as a potential biomarker of cisplatin after intraperitoneal perioperative chemotherapy: a population pharmacokinetic study
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Journal Article
Intraperitoneal clearance as a potential biomarker of cisplatin after intraperitoneal perioperative chemotherapy: a population pharmacokinetic study
2012
Overview
Background:
Intraperitoneal (IP) perioperative chemotherapy with cisplatin is an interesting option in ovarian cancer treatment. A combination of cisplatin with IP epinephrine (already shown to improve IP and decrease systemic platinum (Pt) exposure) was evaluated using a population pharmacokinetic analysis.
Methods:
Data from 55 patients treated with cisplatin-based IP perioperative chemotherapy with (
n
=26) or without (
n
=29) epinephrine were analysed using NONMEM.
Results:
Epinephrine halves clearance between peritoneum and serum (IPCL) and increases the Pt central volume of distribution, IP exposure and penetration in tissue. IPCL has a better predictive value than any other parameter with respect to renal toxicity.
Conclusion:
This confirms that IPCL could be useful in assessing renal toxicity. As IPCL is also linked to tissue penetration and IP exposure, it may be proposed as biomarker. In addition to a Bayesian estimation, we propose a single-sample calculation-way to assess it. Prospective studies are needed to validate IPCL as a biomarker in this context.
Publisher
Nature Publishing Group UK,Nature Publishing Group
Subject
/ Aged
/ Antineoplastic Agents - administration & dosage
/ Antineoplastic Agents - blood
/ Antineoplastic Agents - pharmacokinetics
/ Biological and medical sciences
/ Biomedical and Life Sciences
/ Cisplatin - administration & dosage
/ Cisplatin - pharmacokinetics
/ Drug Administration Schedule
/ Epinephrine - administration & dosage
/ Epinephrine - pharmacokinetics
/ Female
/ Humans
/ Oncology
/ Ovarian Neoplasms - drug therapy
/ Ovarian Neoplasms - pathology
/ Toxicity
/ Tumors
