He Hui, Ma Dejian, Crone Laura Brooks, Butawan Matthew, Meibohm Bernd, Bloomer Richard J, Yates Charles R
Department of Pharmaceutical Sciences, University of Tennessee College of Pharmacy, Memphis, Tennessee.
Cardiorespiratory/Metabolic Laboratory, School of Health Studies, University of Memphis, Memphis, Tennessee.
J Caffeine Res. 2017 Sep 1;7(3):95-102. doi: 10.1089/jcr.2017.0006.
Theacrine, a methylurate class purine alkaloid, triggers diverse pharmacologic responses, including psychostimulatory activity by modulation of adenosinergic and dopaminergic pathways. In a double-blind, placebo-controlled study, theacrine increased energy, concentration, and mood, while reducing fatigue. Because caffeine, a methylxanthine purine alkaloid, is frequently coadministered with theacrine, we sought to determine if a pharmacokinetic and/or pharmacodynamic interaction existed between theacrine and caffeine. Eight healthy adults received theacrine, as TeaCrine (25 or 125 mg), caffeine (150 mg), or a combination of theacrine (125 mg) and caffeine (150 mg) in a randomized, double-blind crossover study. Blood samples were collected over a 24-hour period and analyzed by Liquid chromatrography-mass spectrometry/mass spectrometry (LC-MS/MS) for theacrine, caffeine, and paraxanthine. Pharmacodynamic response markers, heart rate and blood pressure, were recorded. Theacrine pharmacokinetics was similar following administration of theacrine alone. Caffeine coadministration increased maximum plasma concentration and area under the curve of theacrine without altering theacrine half-life. Theacrine had no impact on caffeine or paraxanthine pharmacokinetics. There was no difference between treatment groups with regard to heart rate or systolic/diastolic blood pressure. Coadministration of theacrine and caffeine results in a clinically significant pharmacokinetic interaction, ., increased theacrine exposure. Enhanced oral bioavailability is the most likely mechanism by which caffeine alters theacrine exposure. However, further studies examining the contribution of presystemic elimination mechanisms, for example, efflux transport and/or gut metabolism, to theacrine bioavailability are needed to confirm the exact mechanism(s). Hemodynamic parameters were unaltered despite the pharmacokinetic interaction, suggesting that coadministration of caffeine and theacrine is safe at the doses administered.
茶氨酸，一种甲基尿酸类嘌呤生物碱，能引发多种药理反应，包括通过调节腺苷能和多巴胺能途径产生精神兴奋活性。在一项双盲、安慰剂对照研究中，茶氨酸能增强精力、提高注意力并改善情绪，同时减轻疲劳。由于甲基黄嘌呤类嘌呤生物碱咖啡因常与茶氨酸共同服用，我们试图确定茶氨酸与咖啡因之间是否存在药代动力学和/或药效学相互作用。在一项随机、双盲交叉研究中，8名健康成年人分别服用茶氨酸（茶氨酸产品，25毫克或125毫克）、咖啡因（150毫克）或茶氨酸（125毫克）与咖啡因（150毫克）的组合。在24小时内采集血样，并用液相色谱-质谱联用/质谱（LC-MS/MS）分析茶氨酸、咖啡因和对黄嘌呤。记录药效学反应指标心率和血压。单独服用茶氨酸时，其药代动力学相似。同时服用咖啡因会增加茶氨酸的最大血浆浓度和曲线下面积，但不改变茶氨酸的半衰期。茶氨酸对咖啡因或对黄嘌呤的药代动力学没有影响。各治疗组在心率或收缩压/舒张压方面没有差异。茶氨酸与咖啡因共同给药会导致临床上显著的药代动力学相互作用，即增加茶氨酸的暴露量。口服生物利用度提高是咖啡因改变茶氨酸暴露量最可能的机制。然而，需要进一步研究考察系统前消除机制（如外排转运和/或肠道代谢）对茶氨酸生物利用度的贡献，以确认确切机制。尽管存在药代动力学相互作用，但血流动力学参数未改变，这表明在所用剂量下，咖啡因与茶氨酸共同给药是安全的。
