Dietary supplements and foods can interact with various drugs, leading to possible clinical concerns. This study aimed to investigate the effect of orally administered sinapic acid (SA) on the pharmacokinetics of aripiprazole (APZ) in rats and its possible modulatory effects on hepatic cytochrome P450 (CYP3A2 and CYP2D6) expression in the liver tissues. Single dose and multiple dose parallel groups of wistar rats were categorized into six groups (n = 6 each) which abstained from food for 12 h prior to the experiment, while water was allowed ad libitum. The investigation was carried out for single dose: Group I was treated with normal saline orally for 15 days (normal control). Group II was administered normal saline orally for 15 days and received APZ (3 mg/kg p.o.) on day 15. Group III received SA (20 mg/kg p.o.) for 15 days and received APZ (3 mg/kg p.o.) on day 15. Group IV was treated with SA (20 mg/kg p.o.) for 15 days. For the multiple dose study, Group I was treated with normal saline orally for 15 days (normal control); Group II received APZ (3 mg/kg p.o.) daily for 15 days; Group III was administered with SA (20 mg/kg p.o.) and APZ (3 mg/kg p.o.) for 15 days and Group IV received SA (20 mg/kg p.o.) for 15 days. The group I and IV were kept common in single and multiple dose groups. After last APZ dose, plasma samples were collected and APZ concentrations were determined using an UPLC-MS/MS technique. The pharmacokinetic parameters were calculated using a non-compartmental analysis. The concomitant administration of APZ with SA (as single or multiple dose) resulted in an increase in APZ absorption and a decrease on its systemic clearance. This was associated with a reduction in CYP3A2 and CYP2D6 protein expressions by 33-43% and -71-68% after the single and multiple co-administration, which are two enzymes responsible of the metabolism of APZ. Therefore, a reduction in the metabolic clearance appears to be the mechanism underlying the drug interaction of dietary supplement containing SA with APZ. Therefore, the concomitant administration of SA and APZ should be carefully viewed. Further investigations are required to assess the clinical significance of such observations in humans.

中文翻译：

---

芥子酸对大鼠阿立哌唑药代动力学的影响：可能的食药相互作用

膳食补充剂和食物会与各种药物相互作用，导致可能的临床问题。本研究旨在探讨口服芥子酸 (SA) 对大鼠阿立哌唑 (APZ) 药代动力学的影响及其对肝组织中肝细胞色素 P450 (CYP3A2 和 CYP2D6) 表达的可能调节作用。将单剂量和多剂量平行组的 wistar 大鼠分为六组（每组 n = 6），在实验前 12 小时禁食，同时允许随意饮水。单次给药：I组口服生理盐水15天（正常对照）。第 II 组口服生理盐水 15 天，第 15 天接受 APZ（3 mg/kg po）。第 III 组接受 SA（20 mg/kg po ) 15 天，并在第 15 天接受 APZ (3 mg/kg po)。IV 组用 SA (20 mg/kg po) 治疗 15 天。对于多剂量研究，I组口服生理盐水15天（正常对照）；第 II 组每天接受 APZ (3 mg/kg po)，持续 15 天；第 III 组给予 SA (20 mg/kg po) 和 APZ (3 mg/kg po) 15 天，第 IV 组接受 SA (20 mg/kg po) 15 天。I 组和 IV 组在单剂量组和多剂量组中保持相同。在最后一次 APZ 给药后，收集血浆样品并使用 UPLC-MS/MS 技术确定 APZ 浓度。使用非房室分析计算药代动力学参数。APZ 与 SA（作为单剂量或多剂量）同时给药导致 APZ 吸收增加和全身清除率降低。这与单次和多次共同给药后 CYP3A2 和 CYP2D6 蛋白表达减少 33-43% 和 -71-68% 相关，这两种酶负责 APZ 的代谢。因此，代谢清除率的降低似乎是含有 SA 的膳食补充剂与 APZ 发生药物相互作用的潜在机制。因此，应仔细查看 SA 和 APZ 的同时给药。需要进一步的研究来评估这种观察在人类中的临床意义。代谢清除率的降低似乎是含有 SA 的膳食补充剂与 APZ 发生药物相互作用的潜在机制。因此，应仔细查看 SA 和 APZ 的同时给药。需要进一步的研究来评估这种观察在人类中的临床意义。代谢清除率的降低似乎是含有 SA 的膳食补充剂与 APZ 发生药物相互作用的潜在机制。因此，应仔细查看 SA 和 APZ 的同时给药。需要进一步的研究来评估这种观察在人类中的临床意义。