RESUMO
Pharmacogenetic analysis to explain or predict the response of a specific patient to drug therapy is increasingly used in clinical practice. This holds especially true for CYP genotyping in psychiatry. We present a patient with genetic polymorphisms in more than one CYP450 enzyme, resulting in reduced effectiveness of CYP enzymes, explaining the high drug serum trough levels of antipsychotics and antidepressants and difficulty in optimizing therapy and dosing. Mrs X was found to be a CYP1A2, CYP2D6, CYP3A4 intermediate and in addition a CYP2C19 poor metabolizer. For Mrs X, pharmacogenetic analysis has contributed to reconsider choice and use of medication. Prior knowledge of the genetic polymorphisms in this patient might have avoided treatment delay and discomfort.
Assuntos
Antidepressivos/administração & dosagem , Antipsicóticos/administração & dosagem , Sistema Enzimático do Citocromo P-450/genética , Transtornos Psicóticos/tratamento farmacológico , Antidepressivos/efeitos adversos , Antidepressivos/sangue , Antipsicóticos/efeitos adversos , Antipsicóticos/sangue , Biomarcadores Farmacológicos/sangue , Clozapina/administração & dosagem , Clozapina/efeitos adversos , Clozapina/sangue , Citocromo P-450 CYP1A2/genética , Citocromo P-450 CYP2C19/genética , Citocromo P-450 CYP2D6/genética , Citocromo P-450 CYP3A/genética , Relação Dose-Resposta a Droga , Feminino , Genótipo , Humanos , Pessoa de Meia-Idade , Farmacogenética , Polimorfismo Genético/genética , Transtornos Psicóticos/genética , Transtornos Psicóticos/metabolismo , Transtornos Psicóticos/patologiaRESUMO
Letter in reply to: Eikelenboom-Schieveld SJM, Fogleman JC. Letter to the Editor. Pharmcogenomics 19(14), 1095-1096 (2018) [ 1 ]. Regarding: Ekhart, Matic M, Kant A, van Puijenbroek E, van Schaik R. CYP450 genotype and aggressive behavior on selective serotonin reuptake inhibitors. Phamacogenomics 18(7), 613-620 (2017) [ 2 ].
Assuntos
Sistema Enzimático do Citocromo P-450/genética , Inibidores Seletivos de Recaptação de Serotonina , Agressão , Genótipo , OxirreduçãoRESUMO
AIM: Genetic variants for selective serotonin reuptake inhibitor (SSRI) metabolizing enzymes have been hypothesized to be a risk factor for aggression as adverse drug effect of SSRIs. Our aim was to assess the possible involvement of these polymorphisms on aggression when using SSRIs. MATERIALS & METHODS: A retrospective noninterventional case-control study was performed on 18 cases. The genetic profile of two main genes involved in the metabolism of SSRIs was determined, and predicted phenotype frequencies were compared with Dutch controls and literature data. RESULTS: Predicted CYP2C19 and CYP2D6 phenotypes for all SSRIs analyzed together did not show a significant difference between cases and controls. CONCLUSION: We found no supporting evidence for a significant relationship between CYP2C19 and CYP2D6 polymorphisms, and aggression in patients using SSRIs.
Assuntos
Agressão/fisiologia , Citocromo P-450 CYP2C19/genética , Citocromo P-450 CYP2D6/genética , Variação Genética/genética , Genótipo , Inibidores Seletivos de Recaptação de Serotonina/uso terapêutico , Agressão/efeitos dos fármacos , Agressão/psicologia , Estudos de Casos e Controles , Sistema Enzimático do Citocromo P-450 , Transtorno Depressivo/tratamento farmacológico , Transtorno Depressivo/genética , Transtorno Depressivo/psicologia , Feminino , Humanos , Masculino , Farmacovigilância , Estudos Retrospectivos , Inibidores Seletivos de Recaptação de Serotonina/farmacologiaRESUMO
It has been postulated that the persistent short intravaginal ejaculation latency time (IELT) of men with lifelong premature ejaculation (LPE) is related to 5-hydroxytryptamine (HT)2C receptor functioning. The aim of this study was to investigate the relationship of Cys23Ser 5-HT2C receptor gene polymorphism and the duration of IELT in men with LPE. Therefore, a prospective study was conducted in 64 Dutch Caucasian men with LPE. Baseline IELT during coitus was assessed by stopwatch over a 1-month period. All men were genotyped for Cys23Ser 5-HT2C receptor gene polymorphism. Allele frequencies and genotypes of Cys and Ser variants of 5-HT2C receptor gene polymorphism were determined. Association between Cys/Cys and Ser/Ser genotypes and the natural logarithm of the IELT in men with LPE were investigated. As a result, the geometric mean, median and natural mean IELT were 25.2, 27.0, 33.9 s, respectively. Of all men, 20.0%, 10.8%, 23.1% and 41.5% ejaculated within 10, 10-20, 20-30 and 30-60 s after vaginal penetration. Of the 64 men, the Cys/Cys and Ser/Ser genotype frequency for the Cys23Ser polymorphism of the 5-HT2C receptor gene was 81% and 19%, respectively. The geometric mean IELT of the wildtypes (Cys/Cys) is significantly lower (22.6 s; 95% CI 18.3-27.8 s) than in male homozygous mutants (Ser/Ser) (40.4 s; 95% CI 20.3-80.4 s) (P = 0.03). It is concluded that Cys23Ser 5-HT2C receptor gene polymorphism is associated with the IELT in men with LPE. Men with Cys/Cys genotype have shorter IELTs than men with Ser/Ser genotypes.
