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Among 226 patients treated with icotinib, 71.7%(162/226) developed acquired resistance, and 28.3%(64/226) had primary resistance. Using the specimens at the baseline, there were 13(20.3%) patients with MET amplication, 8(12.5%) patients with BCL2L11 loss (BIM deletion polymorphism), 8(12.5%) patients with PTEN mutations, 6(9.4%) patients with MTOR mutations, 5(7.8%) patients with PIK3CA mutations, 3(4.7%) patients with FGFR3-TACC3 fusion, 2(3.1%) patients with EGFR T790M mutation, 2(3.1%) patients with HER2 amplication, 1(1.6%) patient with MYC amplication, and 16 (25.0%) patients with unknown status. Conclusions: MET amplication, BCL2L11 loss, PI3K-AKT-mTOR signaling pathway (PTEN, MTOR, PIK3CA mutations), FGFR3-TACC3, T790M, HER2 amplication or MYC amplication might contribute to molecular mechanisms of primary resistance to icotinib in EGFR Mþ NSCLC. Further investigations are warranted to overcome these primary resistances. Legal entity responsible for the study: Qu-Xia Zhang. Funding: Has not received any funding.

Cytochrome P450 2D6 (CYP2D6) represents a variety of polymorphism. CYP2D6*10B, an allelic variant shown with a high frequency in Asian compared with Caucasian has been reported to decrease the enzyme activity. The effect of CYP2D6*10B allele was investigated on the pharmacokinetics of chlorpromazine (CPZ) in Korean healthy subjects. Three subjects with wild type, 7 with heterozygous mutation, and 4 with homozygous mutation were participated. Other mutation alleles which may affect this study were excluded. After a single oral administration of CPZ (50mg), blood was serially taken up to 24 hour. Plasma concentrations of CPZ were measured by LC/MS/MS, and pharmacokinetic parameters were calculated by non‐compartmental analyses. Mean peak plasma concentrations in heterozygous and homozygous mutants were 34 and 95% higher than that in wild group (8.7±8.5 ng/ml), respectively. Mean AUCs in both groups increased by 34 and 65% in comparison with that in wild group (60.6±65.8 ng·hr/ml), respectively. However, there was no statistical difference in both parameters due to the extreme interindividual variation. Other pharmacokinetic parameters including elimination rate constant did not show any significant differences among three groups either. CYP2D6*10B mutation seems to increase the plasma concentration of CPZ despite no statistical relevance. Further study in a sufficient number of subjects would be needed including analyses of metabolite profiles. Clinical Pharmacology & Therapeutics (2004) 75, P90–P90; doi: