A Nordmark1, S Lundgren, S Cnattingius, A Rane. 1. Department of Medical Sciences, Clinical Pharmacology, University Hospital, Uppsala University, S-751 85 Uppsala.
Abstract
AIMS: To validate the use of randomly collected urine samples for assessment of cytochrome P4501A2 (CYP1A2) activity based on dietary caffeine (caffeine metabolic ratio, MRcaff ), and to relate the MRcaff to caffeine intake and smoking habits in a larger group of individuals. METHODS: Nineteen healthy volunteers were included in the validation study. Caffeine (100 mg) was ingested and a urine sample was collected after 6 h. Within the following week a random urine sample was collected in the individuals without a preceding test dose of caffeine. Urine samples were analysed for caffeine and its metabolites by h.p.l.c. and the (AFMU+1U+1X)/1,7U metabolic ratio was used to reflect CYP1A2 activity. In an extended investigation of 522 healthy pregnant women the MRcaff was related to intake of caffeine from various sources, and to smoking. RESULTS: The results from the random and standardised sampling methods correlate with each other (correlation coefficient of MRcaff was 0. 91). The MRcaff as assessed by the random sampling method in a larger population was not affected by source or amount of caffeine ingested. Significantly higher MRcaff was found in smokers compared to non-smokers. In the large group of individuals the random sampling method was possible to use in 80% of the cases. In the residual 20% one or several of the metabolite concentrations were too low or unmeasurable. CONCLUSIONS: Our study demonstrates that the random urine caffeine phenotyping method is possible to use in as many as 80% of the individuals when based on dietary caffeine. Our approach should prove applicable in most countries with widely spread caffeine consumption. The method is useful in larger studies of drug metabolising enzyme activities and minimises the time consumption and costs.
AIMS: To validate the use of randomly collected urine samples for assessment of cytochrome P4501A2 (CYP1A2) activity based on dietary caffeine (caffeine metabolic ratio, MRcaff ), and to relate the MRcaff to caffeine intake and smoking habits in a larger group of individuals. METHODS: Nineteen healthy volunteers were included in the validation study. Caffeine (100 mg) was ingested and a urine sample was collected after 6 h. Within the following week a random urine sample was collected in the individuals without a preceding test dose of caffeine. Urine samples were analysed for caffeine and its metabolites by h.p.l.c. and the (AFMU+1U+1X)/1,7U metabolic ratio was used to reflect CYP1A2 activity. In an extended investigation of 522 healthy pregnant women the MRcaff was related to intake of caffeine from various sources, and to smoking. RESULTS: The results from the random and standardised sampling methods correlate with each other (correlation coefficient of MRcaff was 0. 91). The MRcaff as assessed by the random sampling method in a larger population was not affected by source or amount of caffeine ingested. Significantly higher MRcaff was found in smokers compared to non-smokers. In the large group of individuals the random sampling method was possible to use in 80% of the cases. In the residual 20% one or several of the metabolite concentrations were too low or unmeasurable. CONCLUSIONS: Our study demonstrates that the random urine caffeine phenotyping method is possible to use in as many as 80% of the individuals when based on dietary caffeine. Our approach should prove applicable in most countries with widely spread caffeine consumption. The method is useful in larger studies of drug metabolising enzyme activities and minimises the time consumption and costs.
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