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Background: Caffeine elimination and monitoring of its metabolites after a single peroral administration in used to evaluate liver metabolic function. The aim of the study was to use the paraxanthine/caffeine ratio in saliva to evaluate liver function in patients with liver cirrhosis. Results were correlated with various procedures evaluating the elimination rate of caffeine., Methods and Results: The study group consisted of 7 patients with compensated liver cirrhosis and 10 healthy volunteers, all individuals were given a single 280 mg dose of caffeine perorally. Concentration of salivary caffeine was determined in each person with high performance liquid chromatography after 4, 6, 8 and 12 hours after application. The paraxanthine/caffeine ratio was evaluated at the 6-hour interval. Estimated clearance (CL), half-life (t1/2) and volume of distribution (Vd) were calculated from 2 or 4 concentrations of the drug. The metabolic ratio of the patients (x = 0.15 +/- 0.07) was significantly lower then the control group (x = 0.55 +/- 0.29). Using a four-point procedure we acquired the following values: patients--CL 2.39 +/- 2.36 l/h, t1/2 = 90.18 +/- 168.44 h; healthy volunteers--CL = 8.10 +/- 4.58 l/h, t1/2 = 8.60 +/- 4.12 h (p < 0.05). Statistically significant correlation was found between the metabolic ratio and CL value (rs = 0.83) or between half-life (rs = -0.72). Similar results were also obtained using the two-point method., Conclusion: In patients with liver cirrhosis we found significantly lower paraxanthine/caffeine ratio which correlates with lowered elimination of caffeine. Its evaluation enables non-invasive assessment of liver metabolic function from a single sample of saliva.

An in vivo phenotyping method of CYP1A2 (cytochrome P-450 1A2) and NAT2 (N-acetyltransferase, isoform 2) based on caffeine test (Butler et al. Pharmacogenetics 1992;2:116-127) with modifications has been established. Molar concentrations of caffeine and its metabolites in urine were determined by HPLC with gradient elution and spectral detection (200-350 nm). The results obtained with this method were sufficiently accurate and precise and allowed to calculate the respective parameters which were subsequently used to evaluate the CYP1A2 and NAT2 activities.