Cancer Chemotherapy and Pharmacology 2019-Oct
Pharmacokinetics and safety of erlotinib and its metabolite OSI-420 in infants and children with primary brain tumors.
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概要
PURPOSE
Erlotinib (Tarceva®), a potent small molecule inhibitor of the epidermal growth factor receptor tyrosine kinase, has been evaluated to treat infants and children with primary brain tumors. The pharmacokinetics of erlotinib and its primary metabolite OSI-420 were characterized and exposure-safety associations were investigated.RESULTS
Data from 47 patients (0.7-19 years old) were collected and best fitted by one-compartment linear models. Erlotinib and OSI-420 apparent clearances (CL/F and CLm/Fm) were higher in patients < 5 years compared to older patients (mean CL/F: 6.8 vs 3.6 L/h/m2, and mean CLm/Fm: 79 vs 38 L/h/m2, p < 0.001), and were 1.62-fold and 1.73-fold higher in males compared to females (p < 0.01). Moreover, CL/F was 1.53-fold higher in wild-type patients than in patients heterozygous or homozygous mutant for ABCG2 rs55930652 (p < 0.05). Most of the toxicities reported were grade 1. No associations were found between drug pharmacokinetics and drug-induced toxicities.