Faculty of Pharmacy, Universitas Gadjah Mada, Sekip Utara, Yogyakarta 55281, Indonesia.
Department of Pharmacology and Clinical Pharmacy, Faculty of Pharmacy, Universitas Muhammadiyah Purwokerto, Jl. KH. Ahmad Dahlan Dukuhwaluh, Purwokerto 53182, Indonesia.
Molecules. 2022 Oct 14;27(20):6901. doi: 10.3390/molecules27206901.
Co-administered medicinal herbs can modify a drug’s pharmacokinetics (PK), effectiveness, and toxicity. Andrographis paniculata (Burm. f.) ethanolic extract (APE) and andrographolide (AND) (a potent CYP2C9 inducer/inhibitor) can alter the pharmacokinetic parameters of glipizide (GLZ). This study aimed to determine the potential pharmacokinetics of herb−drug interactions between GLZ and APE/AND in the plasma of normal and diabetic rats using the HPLC bioanalysis method. The glipizide bioanalytical method established with RP-HPLC/UV instrument was validated following the EMA guidelines. GLZ was administered alone and in combination with APE or AND to normal and diabetic rats. The GLZ pharmacokinetic parameters were estimated according to the correlation between concentration and sampling time using the PK solver program. A simple and rapid GLZ bioanalysis technique with a lower limit of quantitation of 25 ng/mL was developed and presented the following parameters: accuracy (error ≤ 15%), precision (CV ≤ 15%), selectivity, stability, and linearity (R2 = 0.998) at concentrations ranging 25−1500 ng/mL. APE administration significantly improved the Cmax and AUC0−t/AUC0−∞ GLZ values in normal and diabetic rats (p < 0.05). AND significantly reduced the bioavailability of GLZ in diabetic rats with small values of T 1/2, Cmax, and AUC0−t/AUC0−∞ (p < 0.05). This combination can be considered in administering medications because it can influence the pharmacological effects of GLZ.
合用草药可以改变药物的药代动力学（PK）、疗效和毒性。穿心莲（Burm. f.）乙醇提取物（APE）和穿心莲内酯（AND）（一种有效的 CYP2C9 诱导剂/抑制剂）可以改变格列吡嗪（GLZ）的药代动力学参数。本研究旨在使用 HPLC 生物分析方法，在正常和糖尿病大鼠的血浆中，确定 GLZ 与 APE/AND 之间草药-药物相互作用的潜在药代动力学。采用 RP-HPLC/UV 仪器建立的格列吡嗪生物分析方法，按照 EMA 指南进行了验证。GLZ 单独给药以及与 APE 或 AND 联合给药，用于正常和糖尿病大鼠。根据浓度与采样时间之间的相关性，使用 PK 求解器程序估算 GLZ 的 PK 参数。开发了一种简单快速的 GLZ 生物分析技术，定量下限为 25ng/mL，具有以下参数：准确性（误差≤15%）、精密度（CV≤15%）、选择性、稳定性和线性（R2=0.998），浓度范围为 25-1500ng/mL。APE 给药显著提高了正常和糖尿病大鼠的 GLZ 的 Cmax 和 AUC0-t/AUC0-∞值（p<0.05）。AND 显著降低了糖尿病大鼠的 GLZ 生物利用度，其 T1/2、Cmax 和 AUC0-t/AUC0-∞值较小（p<0.05）。这种联合用药可以考虑用于给药，因为它会影响 GLZ 的药理作用。
