Pharmacokinetics of Chemotherapy Delivered by Ophthalmic Artery Chemosurgery
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Super-selective ophthalmic artery infusion of chemotherapy is a powerful treatment option for intraocular retinoblastoma. However, the dose and schedule for drug administration are selected empirically. Knowledge of the amount of chemotherapy that effectively targets the ocular structures after local delivery and the availability in the bloodstream that correlates with toxicity may provide guidance towards a more scientific approach. The pharmacokinetics of a chemotherapy agent after local delivery is an important concept that has many clinical implications and varies according to drug type and method of delivery. Pharmacokinetic studies have been carried out in different animal models and patients with retinoblastoma. In the present chapter we will discuss general concepts of pharmacokinetics and specifically, we will overview the current knowledge about topotecan and melphalan pharmacokinetics after super-selective ophthalmic artery infusion and the relationship with pharmacodynamic parameters in animals and patients. Differences, advantages and disadvantages of each model will be discussed for a better understanding.
KeywordsPharmacokinetics Topotecan Melphalan Swine model Retinoblastoma
Financial Support: This work was supported by Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET, PIP Nr 11220090100343); Hospital JP Garrahan, Buenos Aires, Argentina; Agencia Nacional de Promoción Científica (PICT 2010-2271); Fund for Ophthalmic Knowledge (GLC, ACF), New York, NY, USA.
Compliance with Ethical Requirements: Dr. Schaiquevich and Dr. Chantada declare that they have no conflict of interest.
The present study followed the tenets of the Declaration of Helsinki and institutional review board approval was obtained. Written informed consent was obtained from the parent/guardian for being included in the study.
All experiments adhered the tenets of Hospital Garrahan Institutional Committee for Animal Care and the ARVO Statement for the use of animals in ophthalmic and vision research. Also, all institutional and national guidelines for the care and use of laboratory animals were followed.
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