BACKGROUND: Imatinib is the standard treatment for patients with gastrointestinal stromal tumors (GISTs), but there is significant variation in imatinib plasma trough concentrations (C min ) among patients. The imatinib C min distribution at different doses and the correlation of adverse reactions with C min in Chinese patients with GIST from a high-volume center were evaluated. METHODS: From July 1, 2017 to December 31, 2018, patients who were receiving imatinib treatment for GIST were prospectively enrolled. Steady-state blood samples were obtained from patients who had received same-dose imatinib treatment for ≥1 month with good compliance. Adverse reactions were recorded during regular follow-up, and blood samples were collected 24 ± 2 hours after dosing. Liquid chromatography-tandem mass spectrometry was used to measure drug concentrations. RESULTS: In total, 307 patients who received 367 dose levels were investigated. The imatinib C min was 1315 ± 716 ng/mL, 2117 ± 597 ng/mL, and 3844 ± 987 ng/mL in patients who were receiving imatinib 400 mg, 600 mg, and 800 mg daily, respectively. The C min was significantly correlated with periorbital and limb edema (P < .001), anemia (P < .001), and rash (P = .037). Nausea and vomiting, diarrhea, and conjunctival hemorrhage also were correlated, but not significantly. A much higher C min was observed with severe adverse reactions. There was no correlation between the imatinib C min and leukopenia, muscle cramps, or hepatobiliary dysfunction. CONCLUSIONS: In Chinese patients with GIST, the imatinib C min was higher than that reported for Western populations, especially at higher doses. The C min was correlated with periorbital and limb edema, anemia, and rash, suggesting that monitoring the imatinib C min should be considered when patients develop severe adverse reactions caused by excessive imatinib plasma concentrations.

Eclipta prostrata (EP) is often prescribed in combination with glucocorticoid to treat glomerular nephritis, nephrotic syndrome, and IgA nephropathy in clinical practice of Traditional Chinese Medicine. Previous studies from our laboratory revealed that coadministration of EP significantly increased the plasma concentration of prednisolone while decreased the level of cotreated prednisone in rats. However, the underlying mechanism remains unclear. 11β-Hydroxysteroid dehydrogenase (11β-HSD) belongs to the family of oxidoreductases that catalyze the interconversion of prednisone to active prednisolone. Therefore, the current study aimed to investigate the effects of EP on the activity and expression of 11β-HSD in rat liver and kidney. The results showed that oral administration of EP significantly increased the activity of 11β-HSD I in the liver and 11β-HSD II in the kidney by employing the microsomal incubation system. Moreover, gene and protein expressions of 11β-HSD I and 11β-HSD II were also increased in rat liver and kidney, respectively. These results suggest that the effects of EP on 11β-HSD may attribute to the mechanism that administration of EP improves the efficacy and reduces adverse drug reactions of glucocorticoid in patients undergoing combinational therapy.

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