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[1-Methyl-C], [3-Methyl-C] and [7-Methyl-C] caffeine were used to investigate demethylation in control rats, and in rats pretreated with phenobarbital or 3-methylcholanthrene, by aCO-exhalation test. Compared to controls, pretreatment with phenobarbital did not enhance demethylation of any of the labelled caffeines. In contrast, induction by 3-methylcholanthrene, presumably of cytochrome P-448, resulted in highly significant increases in peakCO exhalation rates,CO disappearance constants and areas under the exhalation rate - time curves. Based on these results, [7-methyl-C] and [3-methyl-C] caffeine were chosen for assessing the feasibility of a caffeine breath test in man, using 5 normal volunteers and 2 patients with compensated liver cirrhosis.CO exhalation curves in cirrhotics were clearly different from those in normal volunteers, being characterised by a slower rise and a lower specific activity of exhaledCO. Since the variability of the levels of the specific activity in subjects with normal livers suggested the influence of extraneous factors, a second group of normal volunteers, smokers and nonsmokers, was investigated. With either labels, the averageCO exhalation rate was doubled in smokers. From these studies in rats and preliminary results in man it is concluded that specifically labelled caffeine is a suitable and promising substrate for studying demethylation by breath analysis. Presumably, caffeine represents a safe and sensitive indicator of the activity of the cytochrome P-448 system. [ABSTRACT FROM AUTHOR]

Excretion of the major urinary bile alcohol 27-nor-5 beta-cholestane-3 alpha, 7 alpha, 12 alpha, 24,25- pentol, and of cholic, chenodeoxycholic, deoxycholic and lithocholic acid was measured in 24 h urine collections of 10 extensive and seven poor metabolizers of debrisoquine. There was no significant difference of the excretion of these cholesterol metabolites between the two groups, indicating that cholesterol hydroxylation to bile alcohols and bile acids is probably not controlled by the same genes responsible for the 'debrisoquine- type' hydroxylation polymorphism. [ABSTRACT FROM AUTHOR]

A provocation test with nicotinic acid (50 mg intravenously) was performed in 13 patients with Gilbert's syndrome and seven healthy volunteers to investigate the diagnostic value of several test parameters and to correlate them with the bilirubin clearance. The maximal increment of unconjugated serum bilirubin, the retention at four hours, and the area under the bilirubin concentration time curve. (AUC) were measured. Significant differences between patients and controls were found with regard to the AUC (7.95 +/- SD, 3.29 mmol/min/l vs. 3.08 +/- 0.57; P less than 0.001), the increment of unconjugated bilirubin (24.1 +/- 7.1 mumol/l vs. 10.2 +/- 3.2; P less than 0.001) and the retention (77.7 +/- 8.9% vs. 45.8 +/- 27.4%; P less than 0.02). Of those, the AUC discriminated best between patients and controls. Five patients with Gilbert's syndrome had normal serum bilirubin concentrations (less than 17.1 mumol/l = 1 mg%) at the time of the study, but abnormal AUC and bilirubin increment. A significant correlation was found between the bilirubin clearance and the retention (r = -0.96; P less than 0.001) as well as the AUC (r = -0.82; P less than 0.05) but not with the bilirubin increment. This simple test may be used to assess the disturbance of bilirubin clearance in Gilbert's syndrome. [ABSTRACT FROM PUBLISHER]

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