Association of Hepatic Nuclear Factor 4 Alpha Gene Polymorphisms With Free Imatinib Plasma Levels and Adverse Reactions in Chinese Gastrointestinal Stromal Tumor Patients

This study investigated the effect of genetic variants in hepatocyte nuclear factor 4 alpha (HNF4α, encoded by gene NR2A1), a pivotal transcriptional regulator of drug disposition genes, on dose-adjusted IM-free plasma levels and related adverse reactions in Chinese GIST patients. Methods: Five common polymorphisms of NR2A1 (rs3818247, rs1884613, rs2071197, rs2425640, and rs736824) were genotyped in 70 Chinese GIST patients who had been administered IM 300–600 mg/d. The free IM trough plasma levels were determined based on a method of ultrafiltration coupled with high performance liquid chromatography-tandem mass spectrometry. Results: There were wide interpatient variations in free plasma levels of IM (range, 9.50–67.50 ng/mL), in which significant sex differences were observed (P
Source: Therapeutic Drug Monitoring - Category: Drugs & Pharmacology Tags: Original Article Source Type: research