Caffeine breath test

Polybrominated Biphenyls. A recent study has used caffeine as a potential tool to characterize exposure and/or effect of PBBs (Lambert et al. 1990). In this test, caffeine is used as a metabolic probe of cytochrome P-450 isozymes activity from the CYPIA family, which in animals is significantly induced by PBBs (Safe 1984). Tire caffeine breath test (CBT) is primarily useful for detecting induction of CYP1A2 activity in human liver, and for that reason, it also has been used as a marker for exposure to PCBs, CDDs, and CDFs (Lambert et al. 1992). A volunteer population of 50 Michigan subjects with previously high serum PBB levels and 50 with undetectable or low serum levels was compared to a control population not exposed to PBBs (Lambert et al. 1992). Two tests were conducted, the CYP1A2-dependent caffeine... 

Lambert GH, Schoeller DA, Humphrey HEB, et al. 1990. The caffeine breath test and caffeine urinary metabolite ratios in the Michigan cohort exposed to polybrominated biphenyls A preliminary study. Environ Health Perspect 89 175-181. 

Wietholtz H, Voegelin M, Arnaud MJ, et al. Assessment of the cytochrome P-448 dependent liver enzyme system by a caffeine breath test. Eur J Clin Pharmacol 1981 21 53-59. 

Horsmans Y, De Koninck X, Geubel AP, et al. Microsomal function in hepatitis B surface antigen healthy carriers assessment of cytochrome P450 1A2 activity by the 14C-caffeine breath test. Pharmacol Toxicol 1995 77 247-249. 

Rost KL, Brosicke H, Brockmoller J, et al. Increase of cytochrome P450IA2 activity by omeprazole evidence by the 13C-(N-3-methyl)-caffeine breath test in poor and extensive metabolizers of S-mephenytoin. Clin Pharmacol Ther 1992 52 170-180. 

Fontana RJ, Turgeon DK, Woolf TF, et al. The caffeine breath test does not identify patients susceptible to tacrine hepatotoxicity. Hepatology 1996 23 1429-1435. 

In five children, due to receive carbamazepine for epilepsy, the caffeine breath test was carried out before the administration of carbamazepine 200-600 mg and after a minimum of 2-3 weeks therapy (47). The results suggested that carbamazepine induces the metabolism of caffeine by CYP1A2. 

Parker AC, Pritchard P, Preston T, Choonara I. Induction of CYP1A2 activity by carbamazepine in children using the caffeine breath test. Br J Chn Pharmacol 1998 45(2) 176-8. 

Caubet M, Laplante A, Caille J, Brazier J. [ Cjaminopyriine and [ G]caffeine breath test Influence of gender, cigarette smoking and oral contraceptives intake. Isotopes Environ Health Stud 2002 38 71-7. 

Phenytoin can increase the clearance of caffeine, and possibly invalidates the caffeine breath test Whether carbamazepine increases caffeine metabolism is unclear. Valproate appears not to have any effect on caffeine. 

The clearance of caffeine was about twofold higher and its half-life was reduced by about 50% in patients with epilepsy taking phenytoin, when compared with healthy subjects not taking any medications. In the same study, there were no significant differences in caffeine pharmacokinetics between healthy subjects and patients receiving carbamazepine or sodium valproate. Conversely, carbamazepine was considered to have induced the metabolism of caffeine in 5 children with epilepsy, as assessed by the caffeine breath test. In another study in healthy subjects, there was a reduction in the AUC of carbamazepine when it was given with caffeine, but caffeine had no effect on the pharmacokinetics of sodium valproate. ... 

Phenytoin may possibly invalidate the caffeine breath test, but normally no special precautions are needed if both drugs are taken. The interaction between carbamazepine and caffeine requires further study. 

In 5 subjects cimetidine I g daily for 6 days increased the half-life of a single 300-mg dose of caffeine by about 70% and reduced caffeine clearance. In another study, cimetidine 1.2 g daily for 4 days increased the caffeine half-life by 45% in 6 smokers and by 96% in 6 non-smokers. The caffeine clearance was reduced by 31% in the smokers and by 42% in the non-smokers. A further study found that the caffeine half-life was increased by 59% and the clearance decreased by 40% by cimetidine. Conversely, in a further study in children, cimetidine was not found to affect caffeine metabolism as assessed by the caffeine breath test. ... 

From metabolic studies, an isotopic caffeine breath test has been developed that detects impaired liver function using the quantitative formation of labeled carbon dioxide as an index. From the urinary excretion of an acetylated uracil metabolite, human acet-ylator phenotype can be easily identified and the analysis of the ratio of the urinary concentrations of other metabolites represents a sensitive test to determine the hepatic enzymatic activities of xanthine oxidase and microsomal 3-methyl demethylation, 7-methyl demethylation, and 8-hydroxylation. Quantitative analyses of paraxanthine urinary metabolites may be used as a biomarker of caffeine intake. Fecal excretion is a minor elimination route, with recovery of only 2-5% of the ingested dose. 

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