CYP3A Activity in End-of-Life Cancer Patients Measured by 4β-Hydroxycholesterol/cholesterol Ratio, in Men and Women

SIMPLE SUMMARY: The elimination of drugs by enzymes in the liver may be impaired in cancer patients that are close to death (end-of-life). This could cause unwanted side effects or lack of effect of drugs and compromise the quality of life in patients. Blood samples collected in 137 deceased end-of-life cancer patients were analyzed for the marker 4β-hydroxycholesterol/cholesterol (4β-OHC/C), representing the activity of the most important drug eliminating enzyme, CYP3A. In addition, samples from young (n = 280) and elderly (n = 30) controls were analyzed for 4β-OHC/C. The average 4β-OHC/C was higher in male and female end-of-life cancer patients than in young and elderly controls without cancer. This finding may suggest that the ability to eliminate drugs by CYP3A is maintained until end of life and that drugs metabolized by CYP3 may not need dose adjustment or discontinuation in cancer patients close to death. ABSTRACT: More than 50% of all drugs are metabolized by the cytochrome P450 3A enzyme (CYP3A). The aim of this study was to investigate if the CYP3A activity, measured by the endogenous marker 4β-hydroxycholesterol/cholesterol ratio (4β-OHC/C), is changed during the last weeks and days of life in men and women. To this end, serum samples from 137 deceased patients (median age 70 years) collected at a single time point 1–60 days before death, were analyzed and compared to 280 young (median 27 years), and 30 elderly (median age 70 years) non-cancer controls. There were no significant differences in the 4β-OHC/C ratio between men and women in end-of-life patients (p < 0.25). The median 4β-OHC/C was significantly higher in end-of-life male patients compared to both young (p < 0.0001) and elderly (p < 0.05) male controls. In a similar manner, 4β-OHC/C in end-of-life female patients was significantly higher compared to young and elderly female controls, p < 0.0001 and p < 0.001, respectively. There was no significant correlation between 4β-OHC/C and survival time. The results from this study suggest maintained CYP3A activity to the very last days of life and even a capacity of induction of the enzyme in end-of-life cancer patients.