Influence of the antacid Maalox on the pharmacokinetics of capecitabine in cancer patients
Influence of the antacid Maalox on the pharmacokinetics of capecitabine in cancer patients
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DOI：
10.1007/s002800050900
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发表时间：
1999-04-01
影响因子：
3
通讯作者：
Weidekamm, E
中科院分区：
文献类型：
--
作者：
Reigner, B;Clive, S;Weidekamm, E
目的：研究抗酸剂Maalox对卡培他滨(希罗达)及其代谢物在癌症患者体内药代动力学的影响。方法：12例以转移为主的实体肿瘤患者以开放、随机、三方交叉的方式接受单次口服1250 mg/m(2)卡培他滨(A组)、单次1250 mg/m(2)卡培他滨(B组)和单次1250 mg/m(2)卡培他滨(2 h后20 m l)Maalox(C组)治疗。每次给药后连续采集24小时的血样和尿样。不变的卡培他滨及其代谢物在血浆中用液相色谱/质谱仪分析，在尿中用核磁共振波谱分析。结果：Maalox与卡培他滨合用或延迟给药2小时均不影响卡培他滨及其代谢物的血药浓度达峰时间(C-max)和消除半衰期。令人意外的是，当Maalox与Capecitabine一起服用时，观察到卡培他滨和5‘-脱氧-5-氟胞苷的C-max和AUC(0-无穷大)值适度增加。然而，这些增长幅度在10%到31%之间，没有统计学意义(P>；0.05)，也没有临床意义，没有迹象表明其他代谢物5‘-脱氧-5’-氟尿苷(5‘-DFUR)、5-氟尿嘧啶和α-氟-β-丙氨酸的血浆浓度持续变化。这三种代谢物的C-max和AUC(0-无穷大)值以随机的方式增加和减少。这些变化的幅度很低(13%)，在统计上没有显著意义。对5‘-DFUR的AUC值进行初步统计分析，P值为0.4524，表明两种治疗方法之间没有显著差异，加入MALOX对总的尿液回收率或卡培他滨或其代谢物从尿中回收的剂量的比例没有影响。结论：在本研究所用剂量下，MAALOX对卡培他滨的胃肠吸收程度和吸收速率的影响没有临床意义。因此，在接受Maalox治疗的患者中，没有必要调整卡培他滨的给药时机。
Purpose: In the present study the possible influence of the antacid Maalox on the pharmacokinetics of capecitabine (Xeloda) and its metabolites was investigated in cancer patients. Methods: A total of 12 patients with solid, predominantly metastatic tumors of various origin received a single oral dose of 1250 mg/ m(2) of capecitabine (treatment A), a single oral dose of 1250 mg/m(2) of capecitabine followed immediately by 20 ml of Maalox (treatment B), and a single oral dose of 1250 mg/m(2) of capecitabine followed 2 h later by 20 mi of Maalox (treatment C) in an open, randomized, three-way cross over fashion. Serial blood and urine samples were collected for up to 24 h after each administration. Unchanged capecitabine and its metabolites were analyzed in plasma using liquid chromatography/mass spectrometry and in urine using nuclear magnetic resonance spectroscopy. Results: Administration of Maalox either concomitantly with capecitabine or delayed by 2h did not influence the time to peak plasma concentrations (C-max) or the elimination half-lives of capecitabine and its metabolites. Unexpectedly, moderate increases in the C-max and AUC(0-infinity) values obtained for capecitabine and 5'-deoxy-5-fluorocytidine were observed when Maalox was given together with capecitabine. However, these increases, which ranged between 10% and 31%, were not statistically significant (P > 0.05) and are not of clinical significance, There was no indication of consistent changes in the plasma concentrations of the other metabolites 5'-deoxy-5'-fluorouridine (5'-DFUR), 5-fluoroupacil, and alpha-fluoro-beta-alanine. The C-max and AUC(0-infinity) values recorded for these three metabolites increased and decreased in a stochastic manner. The magnitude of these changes was low (< 13%) and not statistically significant. The primary statistical analysis of the AUC(0-infinity), obtained for 5'-DFUR provided a P value of 0.4524 and dearly indicated no significant difference between the treatments, The addition of Maalox had no influence on the overall urinary recovery or the proportion of the dose recovered as capecitabine or its metabolites from urine, Conclusion: At the dose used in this study, the effect of concomitantly delivered Maalox on the extent and rate of gastrointestinal absorption of capecitabine is not clinically significant. Therefore, there is no need to adjust the dose of timing of capecitabine administration in patients treated with Maalox.