***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: The impact of gender , use of oral contraceptive steroids ( OCS )  , coffee consumption and of smoking on the metabolism of sparteine , caffeine , and paracetamol was studied in 194 r and omly selected subjects ( 98 male and 95 female ) . Thirty-eight of the male volunteers were cigarette smokers , 40 of the female subjects were smokers and /or users of OCS .  The metabolic ratio of sparteine oxidation ( MRs ) showed a trimodal distribution . 7.7 % of the subjects had a MRs > 20 and thus were poor metabolizers ( PMs ) . Within the extensive metabolizer ( EM ) subjects , a distinct subgroup accounting for 11 % was observed with 20 > MRs > 1.2 . Six of the 15 phenotypical PMs were heterozygous EMs by genotyping . This indicates the existence of one or several CYP2D6 mutations which can not be identified by the currently employed genotyping methods . In each subgroup , i.e. smokers/OCS and non-smokers/non-OCS , the cumulative frequency distribution of the heterozygous ( wt/B ) phenotype caused a shift to higher MRs compared with the wild-type homozygotes ( wt/wt ) . Thus , for the in vivo activity of CYP2D6 , genetic determinants prevail over environmental factors . Smoking , use of oral contraceptive steroids , caffeine consumption , or gender had no influence on sparteine metabolism . The distribution of the paracetamol glucuronide/paracetamol metabolic ratio appeared to be unimodal although skewed . Glucuronidation capacity was clearly affected by gender , OCS use and smoking . It was higher in male than in female subjects . Male smokers had the highest , and female non-smokers/non-OCS users the lowest metabolic ratio . CYP1A2 activity , as determined by a caffeine metabolic ratio ( ( AFMU + 1X + 1U)/1 , 7U ) , was multimodally distributed and was clearly increased in smokers . It was significantly correlated to paracetamol glucoronidation in male heavy smokers ( r=0.85 ) , suggesting an element of co-regulation of CYP1A2 and of paracetamol conjugating UDP-glucuronosyltransferase isozymes , including UGTI.6 AIMS To study the potential utility of caffeine based probes of CYP1A2 enzyme activity in predicting the pharmokinetics of tacrine in patients with Alzheimer 's disease . METHODS The pharmokinetics of a single 40 mg oral dose of tacrine were measured in 19 patients with Alzheimer 's disease . Each patient also received 2 mg kg(-1 ) [ 13C-3-methyl ] caffeine orally and had breath and urine sample s collected . RESULTS  Tacrine oral clearance ( CL F(-1 ) kg(-1 ) ) , which varied 15-fold among the patients , correlated significantly with the 2 h total production of 13CO2 in breath ( r=0.56 , P=0.01 ) , and with each of two commonly used urinary caffeine metabolite ratios : the ' paraxanthine/caffeine ratio ' ( 1,7X + 1 , 7U)/1,3,7X ) ( r=0.76 , P=0.0002 ) and the ' caffeine metabolic ratio ' ( AFMU + 1X + 1U)/1 , 7U)(r=0.76 , P=0.0001 ) . CONCLUSIONS These observations support a central role for CYP1A2 in the in vivo disposition of tacrine and the potential for drug interactions when tacrine treated patients receive known inducers or inhibitors of this enzyme . The magnitude of the correlations we observed , however , are probably not sufficient to be clinical ly useful in individualizing tacrine therapy 
    Output:
    
Our results indicate the functional importance of −163C > A polymorphism on CYP1A2 inducibility in humans