Fig. 1.
Twelve adult patients with thoracic malignancies were administered mithramycin in a Phase II clinical trial. (A) LFT values were conducted in 20 cycles and analyzed for highest grade toxicity. Pharmacokinetic analysis was conducted, and ALT and AST toxicity grade were plotted vs. (B) Cmax, (C) area under the curve, and (D) clearance. Means are shown by bars. (E) The highest ALT or AST test value for each patient was associated with a combination of two SNPs in ABCB4 (rs2302387) and ABCB11 (rs4668115). (F) Total hepatocyte ABCB4 and ABCB11 gene expression was measured using quantitative PCR and plotted according to combined rs2302387/rs4668115 genotype. (G) Genotype of ABCB11 (rs4668115) was confirmed to be associated with LFT elevations in pediatric patients treated with mithramycin. *P < 0.05 and **P < 0.01.