Abstract
INTRODUCTION: Chemotherapeutic agents are evaluated in at least two animal species prior to evaluation in humans. In children with CNS tumors, the plasma and CSF pharmacokinetics of these agents are derived from models like non-human primates (NHP) to predict CNS penetration. However, the extent to which these NHP parameters accurately predict those observed in clinical trials has not been thoroughly evaluated. The objective of this study was to compare the pharmacokinetics of cytotoxic and cytostatic agents in NHPs and patients to assess the degree of correlation between species. METHODS: A list of known anti-neoplastic agents within the National Cancer Institute’s (NCI) database was compiled, and a literature search for each drug was performed on Scopus, Pubmed, and PsycINFO using keyword combinations “pharmacokinetics,” “non-human primates,” “clinical testing,” and others. The pharmacokinetic parameters AUC, clearance, half-life, peak time (Tmax) and maximum concentration (Cmax) were compared between species using Spearman’s rank correlations. RESULTS: Plasma pharmacokinetic data were obtained for 17 cytotoxic and 6 cytostatic compounds. Rank correlation coefficients (ρ=cytotoxic; cytostatic) were: AUC (0.662; 0.500); Clearance (0.857; 1.000); Half-life (0.632; 0.600); Tmax (0.232; 0.530); and Cmax (0.447; 0.200). CONCLUSION: Interspecies correlations were moderate-to-strongly positive (ρ > 0.50) for AUC, clearance, and half-life, and weak-to-moderate (ρ >0.20 >0.50) for Tmax and Cmax. Interspecies data were only available for a limited number of cytostatic compounds, and no data were available for CSF pharmacokinetic parameters. These findings support the use of NHPs as relevant pharmacokinetic models for chemotherapy agents. Additional studies to assess CSF pharmacokinetics are indicated.