NDLI: Predicting the effects of 8C2, a monoclonal anti-topotecan antibody, on plasma and tissue disposition of topotecan

Content Provider	Springer Nature Link
Author	Shah, Dhaval K. Balthasar, Joseph P.
Copyright Year	2013
Abstract	We are investigating an inverse targeting strategy to reduce the dose limiting systemic toxicities resultant from intraperitoneal administration of topotecan, a model chemotherapeutic drug. This approach utilizes systemic co-administration of anti-topotecan antibodies to alter the plasma and tissue disposition kinetics of topotecan. To better predict the effects of 8C2, a high affinity anti-topotecan monoclonal antibody, on the pharmacokinetics of topotecan, two mathematical models have been developed and evaluated. Model 1 is a hybrid physiologically based pharmacokinetic (PBPK) model that was created by merging a PBPK model for topotecan with a simple two compartment model of 8C2 pharmacokinetics. Model 2 is a comprehensive PBPK model developed by merging a PBPK model for IgG with a PBPK model for topotecan. To help validate the simulation results from both the models, a tissue distribution experiment was conducted, in which topotecan and 8C2 were co-administered in mice. Experimental and simulated data were compared by calculating the median percent prediction error (%PE) for all tissues. For both models, the median %PE values for all the tissues were less than 100 %, indicating that the predicted values were, on average, less than twofold the observed plasma and tissue topotecan concentrations values. In general model 2 was found to be more predictive of the data set than model 1, as the overall median %PE value for model 2 (%PE = 63) was less than model 1 (%PE = 73).
Starting Page	55
Ending Page	69
Page Count	15
File Format	PDF
ISSN	1567567X
Journal	Journal of Pharmacokinetics and Pharmacodynamics
Volume Number	41
Issue Number	1
e-ISSN	15738744
Language	English
Publisher	Springer US
Publisher Date	2013-12-25
Publisher Place	Boston
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	PBPK model Monoclonal antibody Topotecan 8C2 Intraperitoneal chemotherapy Inverse targeting Mathematical modeling Pharmacology/Toxicology Pharmacy Veterinary Medicine Biomedical Engineering Biochemistry
Content Type	Text
Resource Type	Article
Subject	Pharmacology

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