***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: Recently , a novel allelic variant of cytochrome P450 2C19 encoding ultrarapid enzyme activity was described ( denoted CYP2C19 * 17 ) . The objective of this study was to evaluate the impact of CYP2C19 * 17 on serum concentration of escitalopram in psychiatric patients . One hundred and sixty‐six patients treated with escitalopram  were divided into the following subgroups according to CYP2C19 genotype : CYP2C19 * 17/*17 ( n=7 ) , CYP2C19 * 1/*17 ( n=43 ) , CYP2C19 * 1/*1 ( n=60 ) , CYP2C19 * 17/def ( n=16 ) , CYP2C19 * 1/def ( n=34 ) , and CYP2C19def/def ( n=6 ) ( def = defective allele , i.e. , CYP2C19 * 2 or * 3 ) . Dose‐adjusted serum concentrations  of escitalopram were compared using the CYP2C19 * 1/*1 subgroup as reference . Geometric mean of the escitalopram serum concentration was 42 % lower in patients homozygous for CYP2C19 * 17 ( P<0.01 ) and 5.7‐fold higher in subjects homozygous for defective CYP2C19 alleles ( P<0.001 ) . Of the heterozygous subgroups , only CYP2C19 * 1/def was significantly different from CYP2C19 * 1/*1 ( P<0.001 ) . In conclusion , a homozygous CYP2C19 * 17 genotype is associated with lower serum concentration  of escitalopram , which might imply increased risk of therapeutic failure In vitro work shows CYP2C19 and CYP2D6 contribute to the metabolism of escitalopram to its primary metabolite , N-desmethylescitalopram . We report the effect of CYP2C19 and CYP2D6 genotypes on steady state morning concentrations of escitalopram and N-desmethylescitalopram and the ratio of this metabolite to the parent drug in 196 adult patients with depression in GENDEP , a clinical pharmacogenomic trial . Subjects who had one CYP2D6 allele associated with intermediate metabolizer phenotype and one associated with poor metabolizer ( i.e. IM/PM genotypic category ) had a higher mean logarithm escitalopram concentration than CYP2D6 extensive metabolizers ( EMs ) ( p = 0.004 ) . Older age was also associated with higher concentrations of escitalopram . Covarying for CYP2D6 and age , we found those homozygous for the CYP2C19 * 17 allele associated with ultrarapid metabolizer ( UM ) phenotype had a significantly lower mean escitalopram concentration ( 2-fold , p = 0.0001 ) and a higher mean metabolic ratio ( p = 0.0003 ) than EMs , while those homozygous for alleles conferring the PM phenotype had a higher mean escitalopram concentration than EMs ( 1.55-fold , p = 0.008 ) . There was a significant overall association between CYP2C19 genotypic category and escitalopram concentration ( p = 0.0003 ; p = 0.0012 Bonferroni corrected ) . In conclusion , we have demonstrated an association between CYP2C19 genotype , including the CYP2C19 * 17 allele , and steady state escitalopram concentration Sixty-nine depressive patients ( DSM III criteria : 296.2 , 296.3 , 296.5 , 300.4 ) were treated with 40 to 60 mg citalopram ( CIT ) daily for 4 weeks . Among them , 45 responded to treatment ( improvement > 50 % on the 21-item Hamilton Rating Scale for Depression [ HAM-D ] ) and continued their treatment for another week before being released from the study . The 24 nonresponders were r and omized and comedicated under double-blind conditions with lithium carbonate ( Li ) ( 2 x 400 mg/day ) ( CIT-Li group ) or with placebo ( CIT-Pl group ) from days 29 to 35 . For days 36 to 42 , the patients of both subgroups were treated openly with Li ( 800 mg/day ) in addition to the ongoing CIT treatment . On day 35 , 6 of 10 patients responded to the CIT-Li combination , whereas 2 of 14 patients only responded to the CIT-Pl combination . This group difference reached significance ( p < 0.05 ) on day 35 with lower HAM-D total scores in the CIT-Li group . No evidence was seen of a pharmacokinetic interaction between CIT and Li , and this combination was well tolerated . Patients were phenotyped with dextromethorphan and mephenytoin at baseline and at day 28 . As evaluated at baseline , three patients ( responders ) were poor metabolizers of dextromethorphan and six patients ( three responders and three nonresponders ) of mephenytoin . On day 28 , the ratio CIT/N-desmethylCIT ( DCIT ) in plasma was significantly higher in poor than in extensive metabolizers of mephenytoin ( p = 0.0001 ) , and there was a significant positive correlation between the metabolic ratio of dextromethorphan and the ratio DCIT/N-didesmethylCIT in plasma ( p < 0.001 ) . These findings illustrate the role of CYP2D6 and CYP2C19 in the metabolism of  CIT . It can be concluded that Li addition to CIT is effective in patients not responding to CIT alone without any evidence of an accentuation or provocation of adverse events Background Citalopram is a selective serotonin reuptake inhibitor ( SSRI ) mainly prescribed to treat major depression . Objective The aim of this study was to compare the pharmacokinetic characteristics of a new and a br and ed citalopram 20 mg formulation to support the marketing authorization of the test formulation in China . Methods A single-dose , open-label , r and omized-sequence , two-period crossover design was used in this study . Healthy Chinese male cytochrome P450 ( CYP ) 2C19 extensive metabolizers , aged 18–40 years , were eligible to participate . CYP2C19 poor metabolizers were excluded , based on genotyping of genomic DNA from blood sample s. Twenty-four subjects were r and omly assigned to receive the test formulation followed by the reference formulation , and then vice versa . A 2-week washout occurred between study periods . Blood sample s were collected for up to 144 h post-dose . Quantification was carried out using a vali date d high-performance liquid chromatography-t and em mass spectrometry ( HPLC-MS/MS ) method . Pharmacokinetic parameters were calculated and analysed statistically . The two formulations were considered pharmacokinetically equivalent if the 90 % confidence intervals ( CIs ) of the log-transformed ratios ( test/reference ) of the maximum plasma concentration ( Cmax ) , area under the plasma concentration-time curve from time zero to the last measurable concentration ( AUClast ) , and area under the plasma concentration-time curve from time zero to infinity ( AUC∞ ) were within the predetermined acceptance range ( 70–143 % for Cmax ; 80–125 % for AUClast and AUC∞ ) according to China State Food and Drug Administration bioequivalence guidelines . Tolerability was monitored by clinical assessment , vital signs , laboratory analysis and interviews with participants about adverse events . Results A total of 24 participants , with a mean ( SD ) age of 26 ( 3 ) years ( range 22–32 years ) , body weight of 65.2 ( 5.0 ) kg ( range 53–73 kg ) , and height of 172.7 ( 4.9 ) cm ( range 159–182 cm ) , were enrolled in this study . Both formulations showed similar pharmacokinetic profiles . Mean ( SD ) AUClast , AUC∞ and Cmax were 1436 ( 341 ) ng · h/mL , 1595 ( 381 ) ng · h/mL and 32.3 ( 5.9 ) ng/mL , respectively , for the test formulation , and 1444 ( 388 ) ng · h/mL , 1648 ( 504 ) ng · h/mL , 33.1 ( 7.4 ) ng/mL , respectively , for the reference formulation . Median ( range ) time to reach Cmax ( tmax ) was 2 ( 1–12 ) hours ( test ) and 3 ( 1–6 ) hours ( reference ) . The 90 % CIs of the treatment ratios for the ln-transformed values of Cmax , AUClast and AUC∞ were 92.5–103.6 , 95.2–100.6 and 96.4–105.4 , respectively . No significant difference was found between treatments with regard to pharmacokinetic parameters . Fifteen adverse events were reported during the study but none were considered serious . Conclusion This single-dose study found that the test and reference citalopram 20 mg tablets met the regulatory criteria for assuming bioequivalence in the selected healthy Chinese male subjects . Both formulations were well tolerated A single oral dose of omeprazole ( 20 mg ) was given orally to 160 healthy Caucasian Swedish subjects and tested as a probe for CYP2C19 . The study was nonr and omized and included seven subjects previously classified as poor metabolizers ( PM ) of S-mephenytoin . The ratio between the plasma concentrations of omeprazole and hydroxyomeprazole  ( metabolic ratio ; MR ) was determined by HPLC in a blood sample drawn 3 h after drug intake . In 17 subjects the test was repeated and the MRs of omeprazole on the two occasions were correlated ( rs = 0.85 ; p < 0.0001 ) . There was a significant correlation between the MR of omeprazole and the S/R mephenytoin ratio among 141 subjects , in whom both ratios were determined ( rs = 0.63 , p < 0.001 ) . All seven PMs of S-mephenytoin had higher MRs of omeprazole  ( 7.1 - 23.8 ) than extensive metabolizers ( EM ) ( 0.1 - 4.9 ) . All 160 subjects and another 15 Caucasian Swedish PMs previously phenotyped with mephenytoin were analysed with respect to the presence of the CYP2C19m1 allele by PCR amplification of the intron 4/exon 5 junction followed by Sma I digestion . EMs heterozygous for the CYP2C19m1 gene had MRs of omeprazole and S/R ratios of mephenytoin that were higher than those of subjects who were homozygous for the wild-type allele ( p = 0.0001 ) . Nineteen of the 22 PMs were homozygous for the CYP2C19m1 gene . Three were heterozygous for this allele . Thus , 41 of the 44 alleles ( 93 % ) of PMs were defective CYP2C19m1 . One of the remaining three PM alleles was subsequently found to contain the CYP2C19m2 mutation , which has earlier been shown to be associated with the PM phenotype in Oriental population s. In conclusion , the phenotype determined by omeprazole correlated with that of mephenytoin , and was in good agreement with the genotype We investigate the impact of sex and genotype on  citalopram disposition in 35 healthy volunteers who received an oral dose of 20 mg citalopram within a single-dose bioequivalence study . CYP2C19 * 2 and * 3 , and CYP2D6 * 4 mutations were determined by Real-Time PCR . The influence of sex and genotype was analyzed by a linear mixed model for repeated measures , including formulation , period , sequence , sex , CYP2C19 and CYP2D6 as fixed effects and subject nested sequence*sex*CYP2C19*CYP2D6 as the r and om one . Pharmacokinetic parameters were log-transformed and AUC(infinity ) and C(max ) adjusted to the administered dose/weight . The model yields a statistical significance in AUC(infinity ) and CL/F for CYP2C19 and CYP2D6 . Gender , formulation , sequence or period effects were not statistically significant . AUC(infinity ) of CYP2C19 * 1/*2 and CYP2C19 * 2/*2 carriers is 44 % and 118 % higher than wild type , respectively ; CYP2D6 volunteers carrying 1/4 have an AUC 23 % higher than wild type . Our data also suggest that the influence of CYP2D6 on AUC(infinity ) is very low when it is in association with CYP2C19 * 1/*1 while its influence is more apparent in association with CYP2C19 * 1/*2 . In conclusion , we demonstrate the influence of CYP2C19 and CYP2D6 in the disposition of citalopram  , and we suggest 
    Output:
    
In contrast , the exposure to (es)citalopram decreased by 36 % ( 95 % CI 27–46 , p < 0.0001 ) in the UM/UM ( CYP2C19 * 17/*17 ) and by 14 % ( 95 % CI 1–27 , p < 0.05 ) in the UM/EM (CYP2C19 * 17/*1).InterpretationThis is the first meta- analysis based on a systematic review of accumulated information that addresses the relationship between CYP2C19 genotypes and the exposure to citalopram or escitalopram .
All functional CYP2C19 genotype groups demonstrated significant effects on (es)citalopram exposure .
The findings based on our pooled analysis are likely to help in underst and ing the inter-individual variability in the exposure to citalopram and escitalopram in psychiatric patients and to facilitate dose selection , particularly for the homozygous carriers of CYP2C19 * 2 or * 3 ( loss of function ) and CYP2C19 * 17 ( gain of function ) alleles .