Department of Internal Medicine, Takeda General Hospital, Fukushima, Japan.
Department of Internal Medicine, Hirata Central Hospital, Fukushima, Japan.
Cancer Chemother Pharmacol. 2023 Jul;92(1):7-14. doi: 10.1007/s00280-023-04542-7. Epub 2023 May 19.
Fluoropyrimidines are anticancer drugs and can cause hyperammonemia both intravenously and orally. Renal dysfunction may interact with fluoropyrimidine to cause hyperammonemia. We performed quantitative analyses of hyperammonemia using a spontaneous report database to examine the frequency of intravenously and orally administered fluoropyrimidine, the reported frequency of fluoropyrimidine-related regimens, and fluoropyrimidine's interactions with chronic kidney disease (CKD).
This study used data collected between April 2004 and March 2020 from the Japanese Adverse Drug Event Report database. The reporting odds ratio (ROR) of hyperammonemia was calculated for each fluoropyrimidine drug and was adjusted for age and sex. Heatmaps depicting the use of anticancer agents in patients with hyperammonemia were drawn. The interactions between CKD and the fluoropyrimidines were also calculated. These analyses were performed using multiple logistic regression.
Hyperammonemia was observed in 861 of the 641,736 adverse events reports. Fluorouracil was the most frequent drug associated with hyperammonemia (389 cases). The ROR of hyperammonemia was 32.5 (95% CI 28.3-37.2) for intravenously administered fluorouracil, 4.7 (95% CI 3.3-6.6) for orally administered capecitabine, 1.9 (95% CI 0.87-4.3) for tegafur/uracil, and 2.2 (95% CI 1.5-3.2) for orally administered tegafur/gimeracil/oteracil. Calcium levofolinate, oxaliplatin, bevacizumab, and irinotecan were the most frequently reported agents in cases of hyperammonemia with intravenously administered fluorouracil. The coefficient of the interaction term between CKD and fluoropyrimidines was 1.12 (95% CI 1.09-1.16).
Hyperammonemia cases were more likely to be reported with intravenous fluorouracil than orally administered fluoropyrimidines. Fluoropyrimidines might interact with CKD in hyperammonemia cases.
氟尿嘧啶类药物是抗癌药物，无论是静脉内给药还是口服给药都可能导致高氨血症。肾功能障碍可能与氟尿嘧啶相互作用导致高氨血症。我们使用自发报告数据库进行了高氨血症的定量分析，以检查静脉内和口服氟尿嘧啶的频率、氟尿嘧啶相关方案的报告频率以及氟尿嘧啶与慢性肾脏病（CKD）的相互作用。
本研究使用 2004 年 4 月至 2020 年 3 月期间从日本药物不良事件报告数据库收集的数据。计算了每种氟尿嘧啶药物的高氨血症报告比值比（ROR），并按年龄和性别进行了调整。绘制了显示高氨血症患者中使用抗癌药物的热图。还计算了 CKD 与氟尿嘧啶类药物之间的相互作用。这些分析使用多变量逻辑回归进行。
在 641736 份不良事件报告中的 861 份报告中观察到高氨血症。氟尿嘧啶是与高氨血症最相关的药物（389 例）。静脉内给予氟尿嘧啶的高氨血症 ROR 为 32.5（95%CI 28.3-37.2），口服给予卡培他滨的 ROR 为 4.7（95%CI 3.3-6.6），替加氟/尿嘧啶的 ROR 为 1.9（95%CI 0.87-4.3），口服给予替加氟/吉美嘧啶/奥替拉西的 ROR 为 2.2（95%CI 1.5-3.2）。左亚叶酸钙、奥沙利铂、贝伐珠单抗和伊立替康是静脉内给予氟尿嘧啶时高氨血症报告中最常见的药物。CKD 和氟尿嘧啶类药物相互作用项的系数为 1.12（95%CI 1.09-1.16）。
与口服氟嘧啶相比，静脉内氟尿嘧啶更有可能报告高氨血症病例。氟尿嘧啶类药物在高氨血症病例中可能与 CKD 相互作用。
