Fuhr U, Rost K L
Department of Clinical Pharmacology, University Hospital Frankfurt am Main, Germany.
Pharmacogenetics. 1994 Jun;4(3):109-16. doi: 10.1097/00008571-199406000-00001.
Several procedures to monitor CYP1A2 activity in vivo by the use of caffeine as a probe have been proposed. They comprise caffeine clearance, based on both plasma and saliva concentrations, urinary metabolite ratios, the 13C-caffeine breath test, and the paraxanthine/caffeine ratio in plasma. The latter method is fast, simple, economical and restricted to one sampling point. In this study, we retrospectively analysed four clinical trials comprising 78 subjects to validate the use of the paraxanthine/caffeine ratios in plasma and saliva for CYP1A2 activity. The validation was done by correlation of these ratios to the systemic caffeine clearance as a reference method. Additionally, urinary metabolite ratios and the caffeine breath test were included in the analysis. The paraxanthine/caffeine ratios in plasma and saliva preferably 5-7 h after administration of caffeine most closely resembled systemic caffeine clearance with correlation coefficients typically higher than r = 0.85. An equation to estimate systemic caffeine clearance from the paraxanthine/caffeine ratios taken at any time within 3-7 h postdose was developed. Correlations of systemic clearance with urinary metabolite ratios and the caffeine breath test were less reliable both in this investigation and in the literature. In conclusion, the paraxanthine/caffeine ratios in plasma and saliva appear a valid and inexpensive method of assessing CYP1A2 activity in vivo. Apparent distribution of CYP1A2 activity for all healthy subjects appeared bimodal in nonsmokers (n = 29) and smokers (n = 17).
已经提出了几种通过使用咖啡因作为探针在体内监测CYP1A2活性的方法。它们包括基于血浆和唾液浓度的咖啡因清除率、尿代谢物比率、13C-咖啡因呼气试验以及血浆中的副黄嘌呤/咖啡因比率。后一种方法快速、简单、经济且仅限于一个采样点。在本研究中，我们回顾性分析了四项包含78名受试者的临床试验，以验证血浆和唾液中副黄嘌呤/咖啡因比率用于CYP1A2活性的有效性。通过将这些比率与作为参考方法的全身咖啡因清除率进行相关性分析来完成验证。此外，尿代谢物比率和咖啡因呼气试验也纳入了分析。在给予咖啡因后优选5-7小时时，血浆和唾液中的副黄嘌呤/咖啡因比率与全身咖啡因清除率最为相似，相关系数通常高于r = 0.85。建立了一个根据给药后3-7小时内任何时间采集的副黄嘌呤/咖啡因比率来估算全身咖啡因清除率的方程。在本研究以及文献中，全身清除率与尿代谢物比率和咖啡因呼气试验的相关性都不太可靠。总之，血浆和唾液中的副黄嘌呤/咖啡因比率似乎是一种评估体内CYP1A2活性的有效且廉价的方法。所有健康受试者的CYP1A2活性表观分布在非吸烟者（n = 29）和吸烟者（n = 17）中均呈双峰分布。
