From the Department of Clinical Pharmacy (Alshabi, Alkahtani), and from the Department of Pharmacology (Shaikh, Habeeb), College of Pharmacy, Najran University, Najran, Kingdom of Saudi Arabia.
Saudi Med J. 2021 Feb;42(2):151-160. doi: 10.15537/smj.2021.2.25695.
To determine the influence of caffeine on pharmacokinetics and pharmacodynamics of pioglitazone (PIO) in diabetic rats.
This was a preclinical study conducted in the College of Pharmacy, Najran University, Saudi Arabia, using 5 groups of Wistar rats: normal rats, untreated diabetic rats, diabetic rats + caffeine (20 mg/kg), diabetic rats + PIO (10 mg/kg), and diabetic rats + PIO (10 mg/kg) + caffeine (20 mg/kg). The drugs were administered for 14 days, and fasting plasma glucose concentrations were determined on the first day, and thereafter at weekly intervals. On day 14, rat sacrifice was followed with assay of levels of biomarkers. To estimate the pharmacokinetic parameters, the diabetic animals were assigned to 2 groups: one group received PIO (10 mg/kg), while the other received PIO + caffeine (20 mg/kg). Blood samples were drawn from the retro-orbital plexus at different time intervals, and pharmacokinetic parameters were measured using high performance liquid chromatography.
Caffeine caused statistically marked increases in area under the curve, C, T, and half-life of PIO, and decreased clearance. Combination of PIO and caffeine produced a synergistic effect on percentage reduction in blood glucose, with 67.1% reductions observed on day 7 and 68.9% reductions observed on day 14. Liver and cardiac biomarkers were significantly decreased, suggesting cardioprotective and hepatoprotective effects.
Co-administration of PIO with caffeine enhances its antidiabetic effect, probably due to enhanced bioavailability of PIO, leading to clinical benefits in diabetic patients.
研究咖啡因对糖尿病大鼠吡格列酮（PIO）药代动力学和药效学的影响。
这是在沙特阿拉伯纳季兰大学药学院进行的一项临床前研究，使用了 5 组 Wistar 大鼠：正常大鼠、未治疗的糖尿病大鼠、糖尿病大鼠+咖啡因（20mg/kg）、糖尿病大鼠+PIO（10mg/kg）和糖尿病大鼠+PIO（10mg/kg）+咖啡因（20mg/kg）。这些药物连续使用 14 天，在第一天和此后的每周间隔测量空腹血糖浓度。在第 14 天，进行大鼠处死，并测定生物标志物水平。为了估算药代动力学参数，将糖尿病动物分为两组：一组接受 PIO（10mg/kg），另一组接受 PIO+咖啡因（20mg/kg）。从眶后丛采集血样，在不同时间间隔测量药代动力学参数，使用高效液相色谱法。
咖啡因使 PIO 的曲线下面积（AUC）、C、T 和半衰期显著增加，并降低清除率。PIO 和咖啡因联合使用对降低血糖百分比有协同作用，第 7 天降低 67.1%，第 14 天降低 68.9%。肝和心脏生物标志物显著降低，提示具有心脏保护和肝脏保护作用。
PIO 与咖啡因联合使用可增强其抗糖尿病作用，可能是由于 PIO 的生物利用度增强，从而为糖尿病患者带来临床获益。
