Kukongviriyapan Veerapol, Senggunprai Laddawan, Prawan Auemduan, Gaysornsiri Danu, Kukongviriyapan Upa, Aiemsa-Ard Jareerat
Department of Pharmacology and Faculty of Medicine, Khon Kaen University, 40002 Thailand.
Eur J Clin Pharmacol. 2004 Apr;60(2):103-7. doi: 10.1007/s00228-004-0734-3. Epub 2004 Mar 12.
To determine whether caffeine (CA) clearance and salivary paraxanthine (PX)/CA ratio were altered in alcohol-dependent subjects and also whether salivary PX/CA ratio was affected by arylamine-N-acetylation 2 ( NAT-2) genotypes.
Of 30 male individuals recruited in assessing PX/CA ratio and CA clearance by ingestion of CA, 13 were healthy control, 10 were alcohol-dependent subjects with abnormal liver function tests and 7 were alcohol-dependent subjects with normal liver function. CA and PX levels were analysed by means of high-performance liquid chromatography. CA clearance was calculated from concentrations of CA in saliva at various time intervals. In another study, PX/CA ratios were assessed in 46 healthy male subjects. Their NAT2 status was genotyped using polymerase chain reaction with restriction fragment length polymorphism assay.
Salivary CA clearance was well correlated with plasma and salivary PX/CA ratios in a wide range of the clearance. Correlation between salivary PX/CA ratio and CA clearance was considered high from the first hour after CA ingestion and continued so for at least 9 h (r=0.94-0.96, P<0.001). PX/CA ratio in saliva was also well correlated with plasma PX/CA ratio (r=0.98, P<0.001). Salivary CA clearance in the control group was significantly higher than that of patients with abnormal liver function tests, i.e. (mean+/-SEM; 95% confidence limits; l/h/kg) 0.094+/-0.013 (0.064-0.124) and 0.044+/-0.019 (0.002-0.091), respectively, and not different from that of patients with normal liver function tests [0.107+/-0.017 (0.066-0.149)]. Similarly, the same is true for PX/CA ratio. NAT2 genotype status did not apparently affect PX/CA ratio.
Saliva-based PX/CA ratio was a convenient and robust method for assessment of CYP1A2 activity and liver function and it was shown to be altered in alcohol-dependent patients with mild abnormal liver function test.
确定咖啡因（CA）清除率和唾液中副黄嘌呤（PX）/CA比值在酒精依赖者中是否改变，以及唾液中PX/CA比值是否受芳胺 - N - 乙酰化2（NAT - 2）基因型影响。
在通过摄入CA评估PX/CA比值和CA清除率的30名男性个体中，13名是健康对照者，10名是肝功能检查异常的酒精依赖者，7名是肝功能正常的酒精依赖者。CA和PX水平通过高效液相色谱法分析。CA清除率根据不同时间间隔唾液中CA的浓度计算得出。在另一项研究中，对46名健康男性受试者的PX/CA比值进行了评估。使用聚合酶链反应 - 限制性片段长度多态性分析对他们的NAT2状态进行基因分型。
在广泛的清除率范围内，唾液CA清除率与血浆和唾液PX/CA比值密切相关。从摄入CA后的第一小时起，唾液PX/CA比值与CA清除率之间的相关性就很高，并且至少持续9小时（r = 0.94 - 0.96，P < 0.001）。唾液中PX/CA比值与血浆PX/CA比值也密切相关（r = 0.98，P < 0.001）。对照组的唾液CA清除率显著高于肝功能检查异常患者，即（均值±标准误；95%置信区间；l/h/kg）分别为0.094±0.013（0.064 - 0.124）和0.044±0.019（0.002 -0.09），与肝功能检查正常患者[0.107±0.017（0.066 - 0.149）]无差异。同样，PX/CA比值也是如此。NAT2基因型状态显然未影响PX/CA比值。
基于唾液的PX/CA比值是评估CYP1A2活性和肝功能的一种简便且可靠的方法，并且在肝功能轻度异常的酒精依赖患者中显示出改变。
