OBJECTIVES: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.
OBJECTIVES: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.
Authors: Scott D Lane; Charles E Green; Joy M Schmitz; Nuvan Rathnayaka; Wendy B Fang; Sergi Ferré; F Gerard Moeller Journal: J Addict Res Ther Date: 2014