Abstract. In irinotecan (CPT-11)-based chemotherapy, neutropenia and diarrhea are often induced. In the present study, the clinical significance of the concentration ratios of 7-ethyl-10-hydroxycamptothecin (SN-38) glucuronide (SN-38G) and SN-38 in the plasma in predicting CPT-11-induced neutropenia was examined. A total of 17 patients with colorectal cancer and wild-type UDP-glucuronosyltransferase (UGT)1A1 gene were enrolled and treated with CPT-11 as part of the FOLFIRI regimen [CPT-11 and fluorouracil (5-FU)]. Blood was taken exactly 15 min following a 2-h continuous infusion of CPT-11. Plasma concentrations of SN-38, SN-38G and CPT-11 were determined by a modified high-performance liquid chromatography (HPLC) method. The median, maximum and minimum values of plasma SN-38G/SN-38 ratios were 4.25, 7.09 and 1.03, respectively, indicating that UGT activities are variable among patients with the wild-type UGT1A1 gene. The plasma SN-38G/SN-38 ratios decreased with an increase in the trial numbers of chemotherapy (r= 0.741, p= 0.000669), suggesting that CPT-11 treatment suppresses UGT activity, and the low plasma SN-38G/SN-38 ratios resulted in the induction of greater neutropenia. However, in this analysis, 2 clearly separated regression lines were observed between plasma SN-38G/SN-38 ratios and neutropenia induction. In conclusion, UGT activity involved in SN-38 metabolism is variable among patients with the wild-type UGT1A1 gene, and each CPT-11 treatment suppresses UGT activity. One-point determination of the plasma SN-38G/SN-38 ratio may provide indications for the prediction of CPT-11-induced neutropenia and adjustment of the optimal dose, although further studies are required.
Key words:cinacalcet hydrochloride, secondary hyperparathyroidism, adverse event 〈Abstract〉Cinacalcet is an agent used to treat secondary hyperparathyroidism. This drug acts on calcium-sensing receptors in the parathyroid gland to suppress secretion of parathyroid hormone. In past clinical trials, gastrointestinal symptoms and hypocalcemia were the major adverse events reported with cinacalcet. In this study, we surveyed adverse events associated with cinacalcet, in 93 dialysis patients. Cinacalcet significantly / / decreased the median serum intact-parathyroid hormone(i-PTH)level, from 519 pg/mL at baseline to 193 pg/ mL at 21-24 weeks. Adverse events related to cinacalcet were reported in 51 of 93 patients(55%). Gastrointestinal symptoms were the most frequent and were reported in 34 patients, while hypocalcemia was detected in 18 patients. In 17 of the 34 patients, gastrointestinal symptoms occurred within a week after
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