Department of Pharmacy, Radboud University Medical Center, Radboud Institute for Health Sciences, Nijmegen, The Netherlands.
Department of Pharmacy, Ziekenhuis Gelderse Vallei, Ede, The Netherlands.
Int J Cancer. 2021 Jun 1;148(11):2799-2806. doi: 10.1002/ijc.33469. Epub 2021 Jan 19.
Co-treatment with gastric acid suppressants (GAS) in patients taking anticancer drugs that exhibit pH-dependant absorption may lead to decreased drug exposure and may hamper drug efficacy. In our study, we investigated whether a 1-hour time interval between subsequent intake of pazopanib and GAS could mitigate this negative effect on drug exposure. We performed an observational study in which we collected the first steady-state pazopanib trough concentration (C ) levels from patients treated with pazopanib 800 mg once daily (OD) taken fasted or pazopanib 600 mg OD taken with food. All patients were advised to take GAS 1 hour after pazopanib. Patients were grouped based on the use of GAS and the geometric (GM) C levels were compared between groups for each dose regimen. Additionally, the percentage of patients with exposure below the target threshold of 20.5 mg/L and the effect of the type of PPI was explored. The GM C levels were lower in GAS users vs non-GAS users for both the 800 and 600 mg cohorts (23.7 mg/L [95% confidence interval [CI]: 21.1-26.7] vs 28.2 mg/L [95% CI: 25.9-30.5], P = .015 and 26.0 mg/L [95% CI: 22.4-30.3] vs 33.5 mg/L [95% CI: 30.3-37.1], P = .006). Subtherapeutic exposure was more prevalent in GAS users vs non-GAS users (33.3% vs 19.5% and 29.6% vs 14%). Sub-analysis showed lower GM pazopanib C in patients who received omeprazole, while minimal difference was observed in those receiving pantoprazole compared to non-users. Our research showed that a 1-hour time interval between intake of pazopanib and GAS did not mitigate the negative effect of GAS on pazopanib exposure and may hamper pazopanib efficacy.
在服用 pH 依赖性吸收的抗癌药物的患者中，同时使用胃酸抑制剂（GAS）可能会导致药物暴露减少，并可能影响药物疗效。在我们的研究中，我们调查了在随后服用帕唑帕尼和 GAS 之间间隔 1 小时是否可以减轻这种对药物暴露的负面影响。我们进行了一项观察性研究，从每天一次空腹服用 800mg 帕唑帕尼或每天一次随餐服用 600mg 帕唑帕尼的患者中收集了第一个稳态帕唑帕尼谷浓度（C ）水平。所有患者均被建议在服用帕唑帕尼后 1 小时服用 GAS。根据是否使用 GAS 将患者分组，并比较了每个剂量方案下各组的几何均数（GM）C 水平。此外，还探讨了暴露于目标阈值 20.5mg/L 以下的患者比例以及质子泵抑制剂（PPI）类型的影响。与非 GAS 使用者相比，GAS 使用者的 GM C 水平在 800mg 和 600mg 队列中均较低（23.7mg/L [95%置信区间 [CI]：21.1-26.7] 与 28.2mg/L [95% CI：25.9-30.5]，P =.015 和 26.0mg/L [95% CI：22.4-30.3] 与 33.5mg/L [95% CI：30.3-37.1]，P =.006）。与非 GAS 使用者相比，GAS 使用者的治疗药物浓度低于治疗范围的比例更高（33.3%比 19.5%，29.6%比 14%）。亚组分析显示，接受奥美拉唑治疗的患者 GM 帕唑帕尼 C 较低，而与非使用者相比，接受泮托拉唑治疗的患者差异最小。我们的研究表明，在服用帕唑帕尼和 GAS 之间间隔 1 小时并不能减轻 GAS 对帕唑帕尼暴露的负面影响，可能会影响帕唑帕尼的疗效。
