Pedro Dorado

Pedro Dorado
Universidad de Extremadura | UNEX · Department of Medical-Surgery Therapeutics

PhD
0000-0003-4100-721X

About

104
Publications
13,358
Reads
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2,460
Citations
Additional affiliations
March 2016 - present
Universidad de Extremadura
Position
  • Professor (Associate)
December 2009 - February 2016
Universidad de Extremadura
Position
  • Professor (Assistant)
March 2007 - April 2013
Instituto de Salud Carlos III
Position
  • Researcher
Description
  • Investigador Contratado del Programa "Miguel Servet" del ISCIII
Education
June 2003
Universidad de Extremadura
Field of study
  • Pharmacology
September 1992 - December 1997
Universidad de Extremadura
Field of study
  • Biology

Publications

Publications (104)
Article
Full-text available
We aimed to explore the possible influence of CYP2C9 (*2, *3 and IVS8-109 A4T), CYP2C19 (*2, *3 and *17) and ABCB1 (1236C4T, 2677G4A/T and 3435C4T) on phenytoin (PHT) plasma concentrations in 64 Mexican Mestizo (MM) patients with epilepsy currently treated with PHT in mono- (n = 25) and polytherapy (n = 39). Genotype and allele frequencies of these...
Article
Full-text available
Background: A promoter variable number tandem repeat polymorphism (pVNTR) of CYP2C9 is described with three types of fragments: short (pVNTR-S), medium (pVNTR-M) and long (pVNTR-L). The pVNTR-S allele reduces the CYP2C9 mRNA level in the human liver, and it was found to be in high linkage disequilibrium (LD) with the CYP2C9*3 allele in a White Ame...
Article
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Aims: Assess the incidence of COVID-19 during the first wave of the pandemic in 40 hemodialysis units in Spain. Material and methods: We analyzed 396 Rt-PCR performed March 14th to April 28th, 2020 in a cohort of 2398 hemodialysis (HD) patients corresponding to 19 hospital units and 21 satellite centers. Results: We performed Rt-PCR in 14% of the...
Article
Aim: We evaluated the potential influence of genetic ( CYP3A5, EPHX1, NR1I2, HNF4A, ABCC2, RALBP1, SCN1A, SCN2A and GABRA1) and nongenetic factors on carbamazepine (CBZ) response, adverse drug reactions and CBZ plasma concentrations in 126 Mexican Mestizos (MM) with epilepsy. Subjects & methods: Patients were genotyped for 27 variants using TaqMan...
Article
Full-text available
Interethnic variability in the drug-metabolizing capacity of CYP450 enzymes may lead to discrepancies in the relationship between genotypes and phenotypes worldwide. The present study was aimed to analyze for the first time whether there is a relationship between clinically relevant CYP450 genetic polymorphisms and their drug oxidation capacity (me...
Article
Full-text available
Genetic and nongenetic factors may contribute to lamotrigine (LTG) plasma concentration variability among patients. We simultaneously investigated the association of UGT1A1, UGT1A4, UGT2B7, ABCB1, ABCG2, and SLC22A1 variants, as well as antiepileptic drug co-treatment, on LTG plasma concentration in 97 Mexican Mestizo (MM) patients with epilepsy. U...
Article
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Chronic kidney disease (CKD) is a major health problem worldwide and, in Spain, it is present in 15.1% of individuals. CKD is frequently associated with some comorbidities and patients need to be prescribed multiple medications. Polypharmacy increases the risk of adverse drug reactions (ADRs). There are no published studies evaluating the prevalenc...
Article
Background Chronic kidney disease (CKD) is a public health disease that affects 15.1% of the adult population. Although a high prevalence (94.1%) of skin disorders has been detected in people on haemodialysis or with advanced CKD, few studies have analysed foot disorders at initial CKD stages. Objectives To analyse the prevalence of foot disorders...
Conference Paper
Full-text available
Background Methotrexate (MTX) is the DMARD of choice in the treatment of rheumatoid arthritis (RA). There is important variability in its therapeutic response. The identification of genetic factors related to the absorption, metabolism and action of MTX may facilitate a more efficient use. Objectives To study the effect of clinical characteristics...
Conference Paper
Full-text available
Background Methotrexate (MTX) is the DMARD of choice in the treatment of rheumatoid arthritis (RA). Despite an acceptable efficacy, its use is limited by side effects. The most known adverse events (AE) are gastrointestinal, hepatic, and haematological. Objectives To study the effect of clinical characteristics and of different genetic single nucl...
Article
A long-standing question and dilemma in precision medicine is whether and to what extent genotyping or phenotyping drug metabolizing enzymes such as CYP2D6 can be used in real-life global clinical and societal settings. Although in an ideal world using both genotype and phenotype biomarkers are desirable, this is not always feasible for economic an...
Article
Aim: To determine allele and genotype frequencies of genes influencing anti-epileptic drug therapy in Mexican-Mestizo (MM) healthy volunteers, and to evaluate whether these are different from those reported for other populations. Subjects & methods: Thirty-nine variants of CYP3A5, EPHX1, NR1I2, HNF4A, UGT1A1, UGT2B7, ABCC2, RALBP1, SCN1A, SCN2A...
Article
Full-text available
CYP2C9, CYP2C19 and CYP2D6 metabolize around 40 % of drugs and their genes vary across populations. The Costa Rican population has a trihybrid ancestry and its key geographic location turns it into a suitable scenario to evaluate interethnic differences across populations. This study aims to describe the diversity of CYP2C9, CYP2C19 and CYP2D6 poly...
Article
Full-text available
A twofold higher frequency of CYP2D6 ultrarapid metabolizers (estimated from genotype: gUMs) was reported among Ashkenazi Jews (AJ) living in New York (USA) than in other North American Caucasians, which might be important to guide the prescription for CYP2D6 substrates in AJ communities around the world. This study was aimed to determine whether t...
Article
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To analyze the distribution of CYP2D6 variants in two ethnically-related Mexican Native and Mestizo populations cohabitating the same econiche and their relationships with a distant Mestizo community. 314 volunteers were genotyped for CYP2D6 gene variants (*2, *3, *4, *6, *10, *13, *17, *35 and *41) using predesigned TaqMan probes. CYP2D6*5 and CYP...
Article
Aim: The CYP2C9 IVS8-109T allele was recently found to be more frequent among Swedish individuals, who have the highest losartan metabolic ratio (MR; losartan:E-3174). Thus, the influence of the CYP2C9 IVS8-109A>T polymorphism on the losartan MR was evaluated among healthy Ecuadorians. In addition, the frequency of the CYP2C9 IVS8-109A>T polymorph...
Article
Full-text available
Background: Drug-induced liver enzyme abnormalities may indicate hepatic injury. Antipsychotic drugs also may cause increase in the liver enzymes and serum bilirubin levels. The present report evaluates the case of a patient with risperidone-associated hepatocellular damage. Case summary: A 19-year-old Caucasian man was admitted to the Departmen...
Chapter
Genetic polymorphism in the CYP2D6 gene results in a wide variability in CYP2D6 enzymatic activity, resulting in individuals who are poor metabolizers, extensive metabolizers and ultrarapid metabolizers.
Article
Background & aim: The CYP2D6 -1584C>G polymorphism (rs1080985) has been identified as a major factor for CYP2D6 expression and function, with the mutant -1584G promoter type being consistently associated with significantly greater expression than -1584C. It may therefore be associated with ultrarapid metabolism. The objective of the present study...
Article
The variability in the antipsychotic response is, to some extent, genetically determined. Several studies have attempted to establish a role for genetic variation in genes coding pharmacokinetic and pharmacodynamic targets, but to date, no definite genetic predictive marker has been identified. We aimed to explore the putative role of 19 genetic va...
Article
Full-text available
The aims of this study were to evaluate the diclofenac metabolism in Hispanics from Cuba and Spain and its relation to ethnicity, CYP2C9 genotypes and environmental factors. Diclofenac hydroxylation capacity (concentration ratios of diclofenac/metabolites in 8-h urine) was studied in 160 Cuban (classified as 76 Cuban-Whites-CWs and 84 Cuban-Mestizo...
Article
Full-text available
Background: P-glycoprotein is an efflux transporter encoded by the multidrug-resistance MDR-1 gene, which influences the absorption and excretion of a variety of drugs. The relation between quetiapine pharmacokinetics and MDR-1 genetic polymorphisms remains controversial. Therefore, the aim of the present study was to analyze the association betwe...
Article
Full-text available
UDP-glucuronosyltransferase 1A4 (UGT1A4) is a phase II drug-metabolizing enzyme that catalyzes the glucuronidation of many clinically-important drugs. Interethnic differences in the genetic polymorphism of UGT1A4 have been reported; however, there is no information in Mexican Mestizos (MMs) and Spaniards (SPs). Furthermore, MM is an admixed populat...
Article
Full-text available
Tamoxifen is widely used as an antiestrogen for the treatment of estrogen receptor (ER)-positive breast cancer (BC) with proven efficacy to reduce recurrence and mortality. However, approximately 30–50% of patients receiving adjuvant tamoxifen therapy may end up experiencing a relapse of BC and acquired resistance in metastatic disease [1]. Tamoxi...
Article
Full-text available
Prior studies on the association between the CYP2D6 polymorphism and suicide did not explore whether mental and personality disorders mediate this association. The main objective of the present study was to test an association between CYP2D6 polymorphism and mental and personality disorders among suicide attempters. The MINI and the DSM-IV version...
Article
Full-text available
We previously documented the lowest frequency of CYP2C9*2 in Mexican indigenous Tepehuanos followed by Mestizos and Mexican-Americans populations, suggesting a negative correlation between the CYP2C9*2 frequency and the degree of Asian ancestry in indigenous Americans. We determined the influence of ethnic admixture components on the CYP2C9 allele...
Article
CYP2D6 is involved in the metabolism of antidepressants drugs and of the endogenous neurotransmitter serotonin. We have previously shown an increased number of CYP2D6 active alleles, indicative of higher enzyme hydroxylation capacity, among patients with eating disorders. From a population genetic heterogeneity standpoint, there is a need to extend...
Article
Background: Aripiprazole (ARI) is an antipsychotic drug that is metabolized to dehydroaripiprazole (DARI) by CYP2D6. Because of the large interindividual variability in ARI and DARI plasma concentrations, therapeutic drug monitoring may be of use in psychiatric patients during treatment with ARI. The aim of the present study was to develop a simpl...
Conference Paper
Full-text available
Background: The genetics of cytochrome P450 (CYP) enzymes may largely influence the metabolism of some drugs or xenobiotics in humans. However, only genetics cannot explain the whole drug variability phenomena, other factors such as age, diet, disease’s states and concomitant drug treatment may affect CYP enzymes activity. Thus, measuring the actua...
Article
Background: Losartan is metabolized to losartan carboxylic acid (E-3174) by the polymorphic cytochrome CYP2C9. The aim of the study was to develop a high-performance liquid chromatographic (HPLC) method with fluorescence detection for simultaneously measuring losartan and its metabolite E-3174 in urine to evaluate the losartan urinary metabolic ra...
Article
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Molecular Psychiatry publishes work aimed at elucidating biological mechanisms underlying psychiatric disorders and their treatment
Article
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In bioequivalence studies, intra-individual variability (CV(w)) is critical in determining sample size. In particular, highly variable drugs may require enrolment of a greater number of subjects. We hypothesize that a strategy to reduce pharmacokinetic CV(w), and hence sample size and costs, would be to include subjects with decreased metabolic enz...
Article
Meeting report of the "Second Symposium on Pharmacology of Cytochrome P450 and Transporters" organized by the Cuban Society of Pharmacology in collaboration with the European Society of Pharmacogenetics and Theranostics (ESPT) and the Ibero-American Network of Pharmacogenetics and Pharmacogenomics (www.ribef.com). The Symposium covered different to...
Article
Full-text available
Pharmacogenetic studies have shown that genetic defects in drug-metabolizing enzymes encoded by CYP2C9, CYP2C19 genes and by the transporter ABCB1 gene can influence phenytoin (PTH) plasma levels and toxicity. The patient reported here is a 2-year-old girl with a medical history of cryptogenic (probably symptomatic) epilepsy, who had her first foca...
Article
Full-text available
Risperidone non-compliance is often high due to undesirable side effects, whose development is in part genetically determined. Studies with genetic variants involved in the pharmacokinetics and pharmacodynamics of risperidone have yielded inconsistent results. Thus, the aim of this study was to investigate the putative association of genetic marker...
Article
Full-text available
Aim: Among people who die by suicide, an increased frequency of CYP2D6 active gene multiplication has been described. Therefore, the present study analyzed the relationship between the severity of the suicidal intent and CYP2D6 number of active genes among survivors. Materials & methods: A group of 342 individuals were evaluated with Beck Suicid...
Article
Cytochrome P450 2D6 (CYP2D6) genotypes and the dextromethorphan/dextrorphan (DXM/DXT) metabolic ratio (MR), which is a marker of CYP2D6 activity, were studied in 118 unrelated healthy Ecuadorians. Genotyping of CYP2D6 was performed by amplification of entire CYP2D6 gene by XL-PCR for CYP2D6*5 and multiplication alleles and by real time-PCR for CYP2...
Article
Full-text available
Three IL-10 gene promoter single nucleotide polymorphisms -1082G > A, -819C > T and -592C > A and the haplotypes they define in Caucasians, GCC, ACC, ATA, associated with different IL-10 production rates, have been linked to schizophrenia in some populations with conflicting results. On the basis of the evidence of the sex-dependent effect of certa...
Article
Full-text available
Patients treated with antiepileptic drugs can exhibit large interindividual variability in clinical efficacy or adverse effects. This could be partially due to genetic variants in genes coding for proteins that function as drug metabolizing enzymes, drug transporters or drug targets. The purpose of this article is to provide an overview of the curr...
Article
Full-text available
Molecular Psychiatry publishes work aimed at elucidating biological mechanisms underlying psychiatric disorders and their treatment
Article
Full-text available
CYP2D6 genotype and debrisoquine metabolic ratio (MR) were analyzed in 133 Nicaraguan Mestizos (NMs) and 260 Cubans divided into Cuban Mestizos (CMs) and White Cubans (WCs). The frequencies of poor metabolizers (MR12.6) were 6% in NMs, 3.9% in CMs and 5.3% in WCs. The frequencies of ultrarapid metabolizers (MR0.1) were 0% in NMs, 2.3% in CMs and...
Article
How genes affect the response in a patient to a given medication is still poorly understood; the validation of biomarkers and technologies need to be performed. This study aims to determine the analytical characteristics of PHARMAChip(®), a newly developed pharmacogenetic array, and the Spanish population allelic and genotypic frequencies of the ge...
Article
Full-text available
CYP2D6 polymorphism is associated with variability in drug response, endogenous metabolism (that is, serotonin), personality, neurocognition and psychopathology. The relationship between CYP2D6 genetic polymorphism and the risk of eating disorders (ED) was analyzed in 267 patients with ED and in 285 controls. A difference in the CYP2D6 active allel...
Article
Full-text available
The aim of this study was to explain the variability of CYP2D6 activity by the identification of CYP2D6 deletion and multiplications, and the single-nucleotide polymorphisms (SNPs) –1584C→G, 31G→A and 2988G→A in Mexican Mestizo and Tepehuano subjects. One hundred twelve Mestizos and 99 Tepehuano Amerindians were studied, who were previously phenoty...
Chapter
CYP2D6 polymorphism is related to absent (poor metabolizers, PMs) and normal/decreased (extensive metabolizers, including ultrarapid metabolizers) metabolism of clinically important drugs. Moreover CYP2D6 is also involved in the metabolism of endogenous substrates in the brain which appear highly important for psychological functioning that may be...
Article
Full-text available
Earlier we had found that the CYP2C9*2 allelic frequency was lower in Mexican-Americans living in California than in Spaniards (SP). This was assumed to be related to the low CYP2C9*2 and *3 allele frequencies in Orientals. This study was therefore aimed at analyzing whether there were also differences in CYP2C9 allele frequencies between Mexican-T...
Article
Brain-derived neurotrophic factor (BDNF) plays a critical role in the growth, differentiation and survival of neurons in the CNS. Recent research has suggested that BDNF may be implicated in the etiology of mood disorders and schizophrenia, as well as in the therapeutic action of some drugs, such as antidepressants and antipsychotics. This study ai...
Article
The CYP2D6 -1584C>G (rs1080985) polymorphism has been identified as another major factor for CYP2D6 function that is possibly associated with ultrarapid metabolism. The mutant -1584G promoter genotype seems to be consistently related to a higher protein expression than -1584C. However, the impact this SNP in the CYP2D6 promoter region has on plasma...
Article
A lower serotonin/higher dopamine tone in CYP2D6 poor metabolizers (PMs) versus extensive metabolizers (EMs) has been postulated, which is consistent with our prior research showing behavioral traits related to anxiety and impulsivity in PMs. This tone could also be related to PMs vulnerability to cognitive functioning and/or psychopathology. There...
Article
Full-text available
Debrisoquine hydroxylation polymorphism is by far the most thoroughly studied genetic polymorphism of the CYP2D6 drug-metabolizing enzyme. Debrisoquine hydroxylation phenotype has been the most used test in humans to evaluate CYP2D6 activity. Two debrisoquine hydroxylation phenotypes have been described: poor and extensive metabolizers. A group wit...
Article
Our group has previously show that interindividual variability in CYP2D6 hydroxylation capacity was related to personality differences in cognitive social anxiety. Thus, we aimed to analyze whether this relationship between personality and CYP2D6 phenotype and genotype was found in a similar population of healthy volunteers from a different latitud...
Article
CYP2C8 seems to be involved in diclofenac 5-hydroxylation, while, in vitro, the 4'-hydroxylation and 3'-hydroxylation seem to be mediated mainly by CYP2C9. We have demonstrated the relevance of CYP2C9 genotypes for diclofenac 4'-hydroxylation in healthy volunteers, so that the present study was aimed at analyzing the role of both CYP2C8 and CYP2C9...
Article
The CYP2D6 gene is highly polymorphic, causing absent (poor metabolizers), decreased, normal or increased enzyme activity (extensive and ultrarapid metabolizers). The genetic polymorphism of the CYP2D6 influences plasma concentration of a wide variety of drugs metabolized in the liver by the cytochrome P450 (CYP) 2D6 enzyme, including antipsychotic...
Article
Full-text available
CYP2D6 has been suggested to be functionally similar to the dopamine transporter. The present study was aimed at analysing the frequency of CYP2D6 alleles and genotype among schizophrenic patients compared to healthy volunteers. CYP2D6 *3, *4, *5, *6, *10 and duplicated alleles were analysed in 128 unselected schizophrenia inpatients (SP) and 142 u...
Article
In the present study, we aimed to analyze the potential relevance of the polymorphism in the promoter region of the serotonin transporter (SERT or 5-HTT) gene (5-HTTLPR) and the risk of suffering major depression (MDD) in a population of patients previously genotyped for CYP2C9. Seventy white European psychiatric outpatients suffering from MDD and...