Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh, 11451, Saudi Arabia.
Clinical Pharmacy, College of Pharmacy, King Saud University, Riyadh, 11451, Saudi Arabia.
Biomed Pharmacother. 2017 Jun;90:694-698. doi: 10.1016/j.biopha.2017.04.015. Epub 2017 Apr 15.
Herbal medicines, dietary supplements, and other foods may pharmacokinetically and/or pharmacodynamically interact with carbamazepine (CBZ), which could lead to potential clinical consequences. Paeonia emodi (PE) is one of the herbs used as complementary therapy in the treatment of epileptic patients in some cultures, and may also be co-administered with CBZ. This study evaluates the effects of PE on the pharmacokinetics of CBZ and determines a possible mechanism of interaction. Rats were administered vehicle saline or PE (200mg/kg, p.o. daily for 7days), then administered a single CBZ dose (80mg/kg, p.o.) on day 7. Plasma samples were analyzed for CBZ concentrations using a sensitive reversed-phase high-performance liquid chromatography (RP-HPLC) assay. Pharmacokinetic parameters were calculated using non-compartmental analysis. The co-administration of PE with CBZ resulted in increased plasma maximum concentration (C), area under the curve (AUC), and half-life (T), by 14.61%, 48.12%, and 43.72%, respectively. The calculated oral clearance (CL/F) was reduced by 33.54%, while the volume of distribution (V) was unaffected. The PE extract also showed a significant potential to reduce CYP3A and CYP2C protein expression by approximately 50%. Therefore, a reduction in the metabolic capacity responsible for CBZ clearance appears to be the mechanism behind this herb-drug interaction. Consequently, the concomitant administration of PE and CBZ should be viewed cautiously. Further studies are needed to determine the clinical relevance of these observations.
草药、膳食补充剂和其他食物可能会与卡马西平（CBZ）在药代动力学和/或药效学上相互作用，从而导致潜在的临床后果。丹皮酚（PE）是一些文化中用于治疗癫痫患者的补充疗法之一，也可能与 CBZ 同时使用。本研究评估了 PE 对 CBZ 药代动力学的影响，并确定了可能的相互作用机制。大鼠给予载体生理盐水或 PE（200mg/kg，每日 po，共 7 天），然后在第 7 天给予单次 CBZ 剂量（80mg/kg，po）。使用灵敏的反相高效液相色谱（RP-HPLC）测定法分析血浆样品中的 CBZ 浓度。使用非房室分析计算药代动力学参数。PE 与 CBZ 同时给药使血浆最大浓度（C）、曲线下面积（AUC）和半衰期（T）分别增加了 14.61%、48.12%和 43.72%。计算的口服清除率（CL/F）降低了 33.54%，而分布容积（V）不受影响。PE 提取物还显示出显著降低 CYP3A 和 CYP2C 蛋白表达约 50%的潜力。因此，负责 CBZ 清除的代谢能力下降似乎是这种草药-药物相互作用的机制。因此，应谨慎同时使用 PE 和 CBZ。需要进一步的研究来确定这些观察结果的临床相关性。
