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

摘要: 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 co-administration anti-topotecan antibodies alter plasma and tissue disposition kinetics topotecan. To better predict effects 8C2, high affinity monoclonal antibody, on pharmacokinetics two mathematical models have been developed evaluated. Model 1 is hybrid physiologically based pharmacokinetic (PBPK) that was created by merging PBPK for topotecan with simple compartment 8C2 pharmacokinetics. 2 comprehensive IgG help validate simulation results both models, distribution experiment conducted, in which were co-administered mice. Experimental simulated data compared calculating median percent prediction error (%PE) all tissues. For %PE values tissues less than 100 %, indicating predicted were, average, twofold observed concentrations values. In general found be more predictive set 1, as overall value (%PE = 63) (%PE = 73).