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Adaptive control with feedback strategies for suramin dosing.
M R Cooper1, R Lieberman, R V La Rocca
1Clinical Pharmacology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892.
Clinical Pharmacology and Therapeutics
|July 1, 1992
Summary
Suramin, an anti-parasitic drug, shows promise as an antineoplastic agent. A three-compartment pharmacokinetic model is best for managing its plasma concentrations and avoiding neurologic toxicity during cancer treatment.
Area of Science:
- Pharmacology
- Oncology
- Toxicology
Background:
- Suramin, an established antiparasitic drug, is under investigation for anticancer properties.
- Clinical trials aim to optimize suramin dosing, prompted by observed neurologic toxicity linked to plasma concentrations exceeding 350 µg/ml.
Purpose of the Study:
- To evaluate population pharmacokinetic models for controlling plasma suramin concentrations during antineoplastic therapy.
- To determine the optimal model for describing suramin pharmacokinetics in cancer patients.
Main Methods:
- Prospective analysis of two- and three-compartment population pharmacokinetic models.
- Assessment of the relationship between suramin clearance and creatinine clearance.
Main Results:
- A three-compartment model provided the best description of suramin pharmacokinetics.
- No correlation was observed between suramin clearance and creatinine clearance.
- Suramin exhibits low systemic clearance, necessitating individualized dosing.
Conclusions:
- A three-compartment pharmacokinetic model is recommended for therapeutic drug monitoring of suramin in oncology.
- Bayesian methods are suggested for estimating individual pharmacokinetics due to model complexity and low clearance.