Showande Johnson Segun, Igbinoba Sharon Iyobor, Kajula Marena, Hokkanen Juho, Tolonen Ari, Adegbolagun Olayemi Modupe, Fakeye Titilayo Oyelola
Department of Clinical Pharmacy and Pharmacy Administration, Faculty of Pharmacy, University of Ibadan, Ibadan, Nigeria, Phone: +2348027887608.
Department of Clinical Pharmacy and Pharmacy Administration, Faculty of Pharmacy, Obafemi Awolowo University, Ile-Ife, Nigeria.
J Basic Clin Physiol Pharmacol. 2019 Apr 5;30(3):jbcpp-2018-0206. doi: 10.1515/jbcpp-2018-0206.
Background Hibiscus sabdariffa beverage (HSB) is widely consumed as a medicinal herb and sometimes used concomitantly with drugs. This study evaluated the in vitro inhibitory potential of the aqueous extract of H. sabdariffa calyces (AEHS) on selected cytochrome P450 (CYP) isozymes and the effect of HSB on the pharmacokinetics of caffeine in vivo. Methods In vitro inhibitions of eight major CYP isozymes by AEHS were estimated by monitoring CYP-specific model reactions of 10 CYP probe substrates using N-in-one assay method. Subsequently, an open, randomized, two-period crossover design was used to evaluate the effect of HSB on the pharmacokinetics of single-dose 200 mg caffeine in six healthy human volunteers. Blood samples were obtained at specific times over a 24 h period. Probe drugs and metabolites were analyzed in their respective matrices with ultra-performance liquid chromatography/mass spectrometer/mass spectrometer and reversed-phase high-performance liquid chromatography/ultraviolet detection. Results The H. sabdariffa aqueous extract weakly inhibited the selected CYP isozymes in vitro, with IC50 of >100 μgmL-1 in the order of CYP1A2 > CYP2C8 > CYP2B6 >> CYP2D6 > CYP2C19 > CYP3A4 > CYP2A6 > CYP2C9. HSB decreased terminal t1/2 and Tmax of caffeine by 13.6% and 13.0%, respectively, and increased Cmax by 10.3%. Point estimates of primary pharmacokinetic endpoints, Cmax = 1.142 (90% confidence interval (CI) = 0.882, 1.480) and AUC0-∞ = 0.992 (90% CI = 0.745, 1.320), were outside the 90% CI of 0.8-1.25 bioequivalence limits. Conclusion The aqueous extract of H. sabdariffa weakly inhibited eight CYP isozymes in vitro, but HSB modified the exposure to caffeine in human. Caution should be exercised in administering HSB with caffeine or similar substrates of CYP1A2 until more clinical data are available.
玫瑰茄饮料（HSB）作为一种药草被广泛饮用，有时还会与药物同时使用。本研究评估了玫瑰茄花萼水提取物（AEHS）对选定细胞色素P450（CYP）同工酶的体外抑制潜力以及HSB对体内咖啡因药代动力学的影响。方法：采用N合一测定法，通过监测10种CYP探针底物的CYP特异性模型反应，评估AEHS对8种主要CYP同工酶的体外抑制作用。随后，采用开放、随机、两周期交叉设计，评估HSB对6名健康人类志愿者单次服用200 mg咖啡因药代动力学的影响。在24小时内的特定时间采集血样。使用超高效液相色谱/质谱仪/质谱仪和反相高效液相色谱/紫外检测法在各自基质中分析探针药物和代谢物。结果：玫瑰茄水提取物在体外对选定的CYP同工酶有微弱抑制作用，IC50>100μg/mL，抑制顺序为CYP1A2>CYP2C8>CYP2B6>>CYP2D6>CYP2C19>CYP3A4>CYP2A6>CYP2C9。HSB使咖啡因的末端t1/2和Tmax分别降低了13.6%和13.0%，并使Cmax增加了10.3%。主要药代动力学终点的点估计值，Cmax = 1.142（90%置信区间（CI）= 0.882，1.480）和AUC0-∞ = 0.992（90%CI = 0.745，1.320），超出了0.8 - 1.25生物等效性限度的90%CI。结论：玫瑰茄水提取物在体外对8种CYP同工酶有微弱抑制作用，但HSB改变了人体对咖啡因的暴露情况。在有更多临床数据之前，将HSB与咖啡因或CYP1A2的类似底物一起给药时应谨慎。
