Salivary caffeine metabolic ratio in alcohol-dependent subjects.
OBJECTIVE
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.


CONCLUSIONS
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.
Kukongviriyapan
Veerapol
V
Department of Pharmacology and Faculty of Medicine, Khon Kaen University, 40002 Thailand. veerapol@kku.ac.th
Senggunprai
Laddawan
L
Prawan
Auemduan
A
Gaysornsiri
Danu
D
Kukongviriyapan
Upa
U
Aiemsa-Ard
Jareerat
J
D000437:Alcoholism / Q000235:genetics / Q000378:metabolism*; D001191:Arylamine N-Acetyltransferase / Q000235:genetics; D002110:Caffeine / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D019388:Cytochrome P-450 CYP1A2 / Q000378:metabolism; D005838:Genotype; D006801:Humans; D008107:Liver Diseases / Q000378:metabolism; D008111:Liver Function Tests; D008297:Male; D012463:Saliva / Q000378:metabolism*; D012907:Smoking / Q000378:metabolism; D013806:Theophylline / Q000378:metabolism
D002110:Caffeine; D013806:Theophylline; D019388:Cytochrome P-450 CYP1A2; D001191:Arylamine N-Acetyltransferase; C478900:NAT2 protein, human; C021183:1,7-dimethylxanthine