***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: Quetiapine is an atypical antipsychotic used for treatment of schizophrenia . Variability in response to this drug may be associated with pharmacogenetics . The aim of this study was to identify genetic markers related to the pharmacokinetics , pharmacodynamics , and adverse effects of quetiapine . The study population comprised 79 healthy volunteers from two bioequivalence trials who were genotyped to identify polymorphisms in genes encoding enzymes , receptors , and transporters . Quetiapine  plasma levels were quantified using high-performance liquid chromatography/mass spectrometry . Prolactin plasma levels were detected by indirect chemiluminescence . Possible adverse effects were recorded throughout the study . Factors with P value of 0.1 or less in the univariate analysis were included in a multiple regression analysis ( logistic regression for adverse reactions ) . The area under the curve and clearance of quetiapine  were affected by polymorphisms in CYP1A2 and DRD3 , respectively . Men had a lower  quetiapine area under the curve compared with women . Prolactin iCmax was higher in volunteers harboring polymorphisms in CYP2C19 and AGT . An association was detected between polymorphisms in CYP1A1 and CYP2C9 and somnolence . Several polymorphisms are responsible for differences in the pharmacokinetics , pharmacodynamics , and safety of quetiapine in healthy individuals Objectives Hyperprolactinemia is a common side effect of first-generation antipsychotics mediated by antagonism of dopaminergic neurotransmission in the pituitary . Most first-generation antipsychotics are metabolized by CYP2D6 in the liver . Further , CYP2D6 is expressed in the human brain as a 5-methoxyindolethylamine O-demethylase potentially contributing to regeneration of serotonin from 5-methoxytryptamine . As dopaminergic neurotransmission is subject to regulation by serotonin , CYP2D6 may exert a nuanced ( serotonergic ) influence on dopaminergic tone in the pituitary . CYP2D6 * 10 is an allele associated with reduced enzyme function and occurs in high frequency ( about 50 % ) in Asians . We prospect ively evaluated significance of CYP2D6 genetic variation for prolactin response to perphenazine ( a model first-generation antipsychotic ) in Asians . Methods A single oral dose of perphenazine ( 0.1 mg/kg ) or placebo was administered to 22 medication-free nonsmoker healthy male Chinese – Canadian volunteers , following a double-blind within-subject r and omized design . Blood sample s were drawn at baseline and 2 , 3 , 4 , 5 and 6 h after drug administration . Results In volunteers with CYP2D6 * 10/CYP2D6 * 10 genotype , the mean area under curve ( AUC0−6 ) for perphenazine concentration was 2.9-fold higher than those who carry the CYP2D6 * 1 allele ( P<0.01 ) . Notably , volunteers homozygous for CYP2D6 * 10 exhibited a significant reduction ( 66 % ) in mean pharmacodynamic tissue sensitivity as measured by the ( prolactin-AUC0−6/perphenazine-AUC0−6 ) ratio ( P=0.02 ) . Conclusions CYP2D6 genotype is a significant contributor to perphenazine concentration in Chinese – Canadians .  Importantly , prolactin response , when normalized per unit perphenazine concentration , appears to be blunted in volunteers homozygous for CYP2D6 * 10 . We suggest that CYP2D6 genetic variation may potentially influence pharmacodynamic tissue sensitivity in the pituitary , presumably through disposition of an endogenous substrate ( e.g. 5-methoxytryptamine ) The effect of pharmacogenetic testing for CYP450 2D6 and 2C19 on treatment costs have not yet been documented . This study used Danish patient registers to calculate healthcare costs of treating patients with diagnoses within the schizophrenic spectrum for 1 year with or without pharmacogenetic testing for polymorphisms in the genes for the CYP2D6 and CYP2C19 enzymes . In a r and omized , controlled trial , stratified with respect to metabolizer genotype , 104 patients were assigned to treatment based on pharmacogenetic testing and 103 patients to treatment as usual .  R and om exclusion of extensive and intermediate metabolizers was used to increase the frequency of extreme metabolizers ( poor metabolizers and ultrarapid metabolizers for CYP2D6 ) to 20 % in both groups . Cost differences were analysed at several levels including ( i ) overall healthcare expenditure , ( ii ) psychiatric hospital cost ( iii ) nonpsychiatric hospital cost , ( iv ) primary care spending and ( v ) pharmaceuticals . Statistically significant differences in costs of psychiatric care dependent on metabolizer status were found between intervention groups . Pharmacogenetic testing significantly reduced costs among the extreme metabolizers ( poor metabolizers and ultrarapid metabolizers ) to 28 % . Use of primary care services and pharmaceuticals was also affected by the intervention . This study confirms earlier findings that extreme metabolizers ( poor and ultrarapid metabolizers ) incur higher costs than similar patients with a normal metabolizer genotype . However , this study shows that these excess costs can be reduced by pharmacogenetic testing . Pharmacogenetic testing for CYP2D6 and CYP2C19 could thus be considered as a means of curtailing high psychiatric treatment costs among extreme metabolizers Abstract The role of the polymorphic cytochrome P450 2D6 ( CYP2D6 ) in the metabolism of risperidone to its major active metabolite , 9-hydroxyrisperidone ( 9-OH-risperidone ) , has been documented after single oral doses of the drug . In this study , the influence of the CYP2D6 polymorphism on the steady-state plasma concentrations of risperidone and 9-OH-risperidone was investigated . Thirty-seven schizophrenic patients on monotherapy with risperidone , 4–8 mg/day , were genotyped by RFLP and PCR for the major functional variants of the CYP2D6 gene . Steady state plasma levels of risperidone and 9-OH-risperidone were analysed by HPLC . Based on the genotype analysis , three patients were classified as ultrarapid metabolizers ( UM ) with an extra functional CYP2D6 gene , 16 were homozygous extensive metabolizers ( EM ) , 15 heterozygous EM and three poor metabolizers ( PM ) . The median steady-state plasma concentration-to-dose ( C/D ) ratios of risperidone were 0.6 , 1.1 , 9.7 and 17.4 nmol/l per mg in UM , homozygous EM , heterozygous EM and PM , respectively , with statistically significant differences between PM and the other genotypes ( P<0.02 ) . The C/D of 9-OH-risperidone also varied widely but was not related to the genotype . The risperidone/9-OH-risperidone ratio was strongly associated with the CYP2D6 genotype , with the highest ratios in PM ( median 0.79 ) . Heterozygous EM also had significantly higher ratios than homozygous EM ( median value 0.23 versus 0.04 ; P<0.01 ) or UM ( median 0.03 ; P<0.02 ) . No significant differences were found in the C/D of the sum of the plasma concentrations of risperidone and 9-OH-risperidone between the genotype groups . In conclusion , the steady-state plasma concentrations of risperidone and the risperidone/9-OH-risperidone ratio are highly dependent on the CYP2D6 genotype . However , as risperidone and 9-OH-risperidone are considered to have similar pharmacological activity , the lack of relationship between the genotype and the sum of risperidone and 9-OH-risperidone indicates that the CYP2D6 polymorphism may be of limited importance for the clinical outcome of the treatment OBJECTIVE The prevalence of hyperprolactinemia during treatment with  conventional antipsychotic drugs or risperidone is under-recognized and requires further investigation . This open-label study was design ed to determine the extent of this potential problem in a routine clinical setting . METHODS Four hundred and two adult in patients or out patients with a diagnosis of schizophrenia , schizophreniform disorder , or schizoaffective disorder were studied in a 1-day , point prevalence trial . Neither clinicians nor patients had any prior knowledge of serum prolactin levels or any potential associated adverse events , and patients were required to have been treated with a conventional antipsychotic drug or risperidone for a minimum of 3 months prior to study entry . Patients taking concomitant medications known to elevate prolactin were excluded . Rigorous assessment of serum prolactin was performed to estimate the prevalence rate of hyperprolactinemia , defined as a level above the upper limit of normal ( > 18.77 ng/ml for males , and > 24.20 ng/ml for females ) . Patients were stratified within antipsychotic treatment by gender and , for females , by menopausal status . RESULTS Serum prolactin was obtained from 147 females ( age range : 21 - 69 years ; mean age=44.51 years ) and 255 males ( age range : 18 - 66 years ; mean age=40.76 years ) . The prevalence of hyperprolactinemia among women of reproductive age ( n=90 ) was 65.6 % ( mean serum prolactin=69.0 ng/ml ) , and among postmenopausal women ( n=51 ) , it was 45.1 % ( mean serum PRL=49.0 ng/ml ) . The prevalence of hyperprolactinemia across all males ( n=255 ) was 42.4 % ( mean serum PRL= 32.4 ng/ml ) . The prevalence of hyperprolactinemia among females taking risperidone ( N=42 ) was 88 % versus 47.6 % of those taking conventional antipsychotic drugs ( N=105 ) , with 48 % of those females of reproductive age on risperidone experiencing abnormal menstrual cycles ( secondary amenorrhea , oligomenorrhea , or polymenorrhea ) . Of all premenopausal females with hyperprolactinemia , 31.6 % had estradiol levels < or=19.8 pg/ml ( which is the mean estradiol level in postmenopausal female patients with normal prolactin ) . Across both genders , there were trends of low key reproductive hormone levels associated with prolactin elevations . Additionally , there was a trend correlation ( p=0.064 ) between prolactin concentration and the risk of menstrual abnormality among females of reproductive age . CONCLUSIONS Hyperprolactinemia is very prevalent among women and men treated with conventional antipsychotic medications or risperidone . Due to the adverse effects associated with hyperprolactinemia , this likelihood should be seriously considered when choosing an antipsychotic suitable for the patient Part I of this article discussed the potential functional importance of genetic mutations and alleles of the human cytochrome P450 2D6 ( CYP2D6 ) gene . The impact of CYP2D6 polymorphisms on the clearance of and response to a series of cardiovascular drugs was addressed . Since CYP2D6 plays a major role in the metabolism of a large number of other drugs , Part II of the article highlights the impact of CYP2D6 polymorphisms on the response to other groups of clinical ly used drugs . Although clinical studies have observed a gene-dose effect for some tricyclic antidepressants , it is difficult to establish clear relationships of their pharmacokinetics and pharmacodynamic parameters to genetic variations of CYP2D6 ; therefore , dosage adjustment based on the CYP2D6 phenotype can not be recommended at present . There is initial evidence for a gene-dose effect on commonly used selective serotonin reuptake inhibitors ( SSRIs ) , but data on the effect of the CYP2D6 genotype/phenotype on the response to SSRIs and their adverse effects are scanty . Therefore , recommendations for dose adjustment of prescribed SSRIs based on the CYP2D6 genotype/phenotype may be premature . A number of clinical studies have indicated that there are significant relationships between the CYP2D6 genotype and steady-state concentrations of perphenazine , zuclopenthixol , risperidone and haloperidol .  However , findings on the relationships between the CYP2D6 genotype and parkinsonism or tardive dyskinesia treatment with traditional antipsychotics are conflicting , probably because of small sample size , inclusion of antipsychotics with variable CYP2D6 metabolism , and co-medication . CYP2D6 phenotyping and genotyping appear to be useful in predicting steady-state concentrations of some classical antipsychotic drugs , but their usefulness in predicting clinical effects must be explored . Therapeutic drug monitoring has been strongly recommended for many antipsychotics , including haloperidol , chlorpromazine , fluphenazine , perphenazine , risperidone and thioridazine , which are 
    Output:
    
We found no significant differences in prolactin levels between CYP2D6 metabolic groups .
Current evidence does not support using CYP2D6 genotyping to reduce risk of antipsychotic-induced hyperprolactinemia .