NDLI: Nontoxic Suramin as a Chemosensitizer in Patients: Dosing Nomogram Development

Content Provider	Springer Nature Link
Author	Chen, Danny Song, Sae Heum Wientjes, M. Guillaume Yeh, Teng Kuang Zhao, Liang Villalona Calero, Miguel Otterson, Gregory A. Jensen, Rhonda Grever, Michael Murgo, Anthony J. Au, Jessie L S.
Copyright Year	2006
Abstract	We reported that suramin produced chemosensitization at nontoxic doses. This benefit was lost at the ∼10-fold higher, maximally tolerated doses (MTD). The aim of the current study was to identify in patients the chemosensitizing suramin dose that delivers 10–50 μM plasma concentrations over 48 h.Nonsmall cell lung cancer patients were given suramin, paclitaxel, and carboplatin, every 3 weeks. The starting chemosensitizing suramin dose was estimated based on previous results on MTD suramin in patients, and adjusted by using real-time pharmacokinetic monitoring. A dosing nomogram was developed by using population-based pharmacokinetic analysis of phase I results (15 patients, 85 treatment cycles), and evaluated in phase II patients (19 females, 28 males, 196 treatment cycles).The chemosensitizing suramin dose showed a terminal half-life of 202 h and a total body clearance of 0.029 L h$^{−1}$ m$^{−2}$ (higher than the 0.013 L h$^{−1}$ m$^{−2}$ value for MTD of suramin). The dosing nomogram, incorporating body surface area as the major covariate of intersubject variability and the time elapsed since the previous dose (to account for the residual concentrations due to the slow elimination), delivered the target concentrations in >95% of treatments.The present study identified and validated a dosing nomogram and schedule to deliver low and nontoxic suramin concentrations that produce chemosensitization in preclinical models.
Starting Page	1265
Ending Page	1274
Page Count	10
File Format	PDF
ISSN	07248741
Journal	Pharmaceutical Research
Volume Number	23
Issue Number	6
e-ISSN	1573904X
Language	English
Publisher	Springer-Verlag
Publisher Date	2006-05-25
Publisher Place	New York
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	chemosensitization dosing nomogram neoplasms suramin Pharmacology/Toxicology Pharmacy Biochemistry Medical Law Biomedical Engineering
Content Type	Text
Resource Type	Article
Subject	Organic Chemistry Pharmacology Molecular Medicine Pharmacology (medical) Biotechnology Pharmaceutical Science

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