The effect of smoking on caffeine elimination was measured in 7 healthy volunteers and in 18 smoking and in 30 nonsmoking patients with alcoholic liver cirrhosis following oral application of 366 mg caffeine. In an intraindividual experiment in smoking health probands, caffeine clearance decreased from 118 +/- 33 to 77 +/- 22 ml per min (p less than 0.05) after abstaining cigarette smoking for 3 weeks. In a control group without liver disease (8 smokers, 15 nonsmokers), we found a caffeine clearance of 114 +/- 40 ml per min in smokers and 64 +/- 20 in nonsmokers (p less than 0.05). Smoking and nonsmoking patients with alcoholic liver cirrhosis did not differ with respect to clinical and laboratory data and hexobarbitone elimination. However, caffeine clearance was 63 +/- 63 ml per min in smoking patients compared to 34 +/- 49 ml per min in nonsmokers (p less than 0.05). Fasting plasma concentrations of caffeine were higher in nonsmokers (5.1 +/- 6.2 micrograms per ml) than in smokers (2.1 +/- 4.5 micrograms per ml, p less than 0.05). We conclude that smoking habits have to be taken into account if caffeine is used as a model compound for measuring quantitative liver function.
Key Words:Gas liquid chromatography (GLC) Fused silica capillary columns Alkali flame ionization detection (AFID) Mass spectrometry (MS) Quantitation in human serum Ethylenediamine Aminophylline Small molecular weight amines and diamines rn-Toluoyl derivatives
SummaryA specific and sensitive method for the determination of ethylenediamine in human plasma is described. The aqueous sample is treated with rn-toluoyl chloride, yielding the N,N'-bis(mtoluoyl) derivative of the diamine, which is extracted into dichloromethane and quantitated after "on column" methylation by capillary gas liquid chromatography with alkali flame ionization detection. The corresponding derivative of putrescine serves as internal standard. The assay is reproducible and calibration curves are linear over the concentration range 0.05 to 10 pg ml-'. The lower detection limit is about 10 ngem1-l. The structures of the compounds of interest eluting from the capillary column are examined by gas liquid chromatography/ mass spectrometry. The assay has been applied to the analysis of ethylenediamine in plasma following the administration of aminophylline and ethylenediamine in a cross-over study to patients with bronchopulmonary diseases. The method also proves suitable for measuring other primary and secondary amines and diamines in aqueous solutions by gas liquid chromatography.
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