Caffeine elimination test

Selection criteria for liver tests 92 9.5 Caffeine elimination test (CET) 109... 

Wang, T., Kleber, G., Stellaard, F., Baumgartner, G. Caffeine elimination a test of liver function. Klin. Wschr. 1985 63 1124-1128... 

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. 

Walton et al. (2001a) examined data for compounds eliminated by the cytochrome P450 isoenzymes CYP1A2 in humans. Absorption, bioavailabihty, and route of excretion were generally similar between humans and the test species for each of the substances (caffeine, paraxanthine, theobromine, and theophylline). However, interspecies differences in the route of metabolism, and the enzymes involved in this process, were identified. The magnitude of difference in the internal dose, between species, showed that values for the mouse (10.6) and rat (5.4) exceeded the fourfold default factor for toxicokinetics, whereas the rabbit (2.6) and the dog (1.6) were below this value. 

Affinity of MIP towards the target analyte should be examined prior to fabrication of the chemosensor. Batch binding assays are used to test selectivity of suitable MIPs. Especially, affinity of MIP to compounds, which are structurally related to the target analyte, should be tested. If MIP binds similarly with these compounds as the template, then cross-reactivity is manifested [156], This effect was exploited for determination of adenine and its derivatives with the use of MIP templated with 9-ethyladenine. Nevertheless, the cross-reactivity, if undesired, can be avoided by suitable sample pretreatment, e.g. by interferant extraction with a supported liquid membrane (SLM) coupled to the MIP-PZ chemosensor. The Fluoropore membrane filter of submicrometre porosity can serve that purpose. That way, this membrane holds interferants, thus eliminating the matrix effect. The SLM-involving determination procedure is cheaper than traditional laborious sample pretreatment used to remove the interfering substances. For instance, caffeine [143] and vanillin [157] in food samples have been determined using this procedure. 

Nagel RA, Dirix LY, Hayllar KM, et al. Use of quantitative liver function tests— caffeine clearance and galactose elimination capacity—after orthotopic liver transplantation. J Hepatol 1990 10 149-157. 

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