Edoardo Spina

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OBJECTIVE Our objective was to determine the influence of cytochrome P450 (CYP) 2C9 and CYP2C19 genetic polymorphisms on warfarin dose requirement and metabolic clearance. METHODS The study population consisted of 93 Italian outpatients receiving long-term warfarin anticoagulant therapy (international normalized ratio values, 2-3), divided into 3 dose(More)
The polymorphic cytochrome P450 isoenzymes (CYPs) 2C9, 2C19 and 2D6 metabolise many important drugs, as well as other xenobiotics. Their polymorphism gives rise to important interindividual and interethnic variability in the metabolism and disposition of several therapeutic agents and may cause differences in the clinical response to these drugs. In this(More)
AIMS CYP2C9 is a major enzyme in human drug metabolism and the polymorphism observed in the corresponding gene may affect the therapeutic outcome during treatment with several drugs. The distribution of variant CYP2C9 alleles was therefore investigated in an Italian and an Ethiopian population. METHODS Allele-specific PCR analysis was carried out in order(More)
OBJECTIVE This review aimed to provide distinct dose recommendations for antidepressants based on the genotypes of cytochrome P450 enzymes CYP2D6 and CYP2C19. This approach may be a useful complementation to clinical monitoring and therapeutic drug monitoring. METHOD Our literature search covered 32 antidepressants marketed in Europe, Canada, and the(More)
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(More)
BACKGROUND The second-generation antidepressants include selective serotonin reuptake inhibitors (SSRIs), serotonin and norepinephrine reuptake inhibitors (SNRIs), and other compounds with different mechanisms of action. All second-generation antidepressants are metabolized in the liver by the cytochrome P450 (CYP) enzyme system. Concomitant intake of(More)
Newer antipsychotics introduced in clinical practice in recent years include clozapine, risperidone, olanzapine, quetiapine, sertindole, ziprasidone, aripiprazole and amisulpride. These agents are subject to drug-drug interactions with other psychotropic agents or with medications used in the treatment of concomitant physical illnesses. Most pharmacokinetic(More)
Carbamazepine is one of the most commonly prescribed antiepileptic drugs and is also used in the treatment of trigeminal neuralgia and psychiatric disorders, particularly bipolar depression. Because of its widespread and long term use, carbamazepine is frequently prescribed in combination with other drugs, leading to the possibility of drug interactions.(More)
The distribution of the oxidation polymorphism related to cytochrome CYP2D6 (debrisoquine type) was determined in 246 healthy Italian volunteers. Phenotyping was based on HPLC determination of the dextrometorphan/dextrorphan concentration ratio (metabolic ratio) in urine samples collected over an 8 h interval following a single oral 30 mg dose of(More)
Risperidone is metabolized to its active metabolite, 9-hydroxyrisperidone, mainly by the cytochrome P450 enzymes CYP2D6 and 3A4. Its antipsychotic effect is assumed to be related to the active moiety, that is, the sum of risperidone and 9-hydroxyrisperidone. Both risperidone and 9-hydroxyrisperidone are substrates of P-glycoprotein (P-gp), a transport(More)