Jorge Duconge

Jorge Duconge
University of Puerto Rico, Medical Sciences Campus · Department of Pharmaceutical Sciences

PhD, MS, BSc Pharm

About

196
Publications
74,170
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Introduction
Jorge Duconge currently works at the Department of Pharmaceutical Sciences, University of Puerto Rico, Medical Sciences Campus (Professor, Lab Director). Jorge does research in Pharmacogenomics, Precision Medicine, PK/PD and Clinical Pharmacology. His current projects are "Adopting a Precision Medicine Paradigm in Puerto Rico: leveraging ancestral diversity to identify predictors of Clopidogrel response in Caribbean Hispanics" (Role: PI; grant #2U54 MD007600-31, NIMHD, NIH) and "A Genomic Approach to Warfarin Dose Prescription in Admixed Caribbean Hispanics" (Role: PI; grant #HL123911, NHLBI, NIH). His current research interest also includes admixture mapping, GWAS, genomic structure of Caribbean Hispanic populations, PK/PD modeling, and pharmacometrics of biotech-derived drug products.
Additional affiliations
December 2004 - present
University of Puerto Rico, Medical Sciences Campus
Position
  • Professor

Publications

Publications (196)
Article
Full-text available
Clopidogrel, a prescription drug to reduce ischemic events in cardiovascular patients, has been extensively studied in mostly European individuals but not among Caribbean Hispanics. This study evaluated the low abundance and reduced activity of paraoxonase-1 (PON1) in clopidogrel-resistant patients as a predictive risk biomarker of poor responders...
Article
Full-text available
Objectives To assess whether genotype-guided selection of oral antiplatelet drugs using a clinical decision support (CDS) algorithm reduces the rate of major adverse cardiovascular and cerebrovascular events (MACCEs) among Caribbean Hispanic patients, after 6 months. Design An open-label, multicentre, non-randomised clinical trial. Setting Eight...
Preprint
Full-text available
Clopidogrel; a prescription drug to reduce ischemic events in cardiovascular patients; has been extensively studied in mostly European individuals but not among Caribbean Hispanics. This study evaluated the low abundance and reduced activity of paraoxonase-1 (PON1) in clopidogrel-resistant patients as a predictive risk biomarker of poor responders...
Article
Full-text available
The Pharmacogene Variation Consortium (PharmVar) serves as a global repository providing star (*) allele nomenclature for the polymorphic human CYP4F2 gene. CYP4F2 genetic variation impacts the metabolism of vitamin K, which is associated with warfarin dose requirements, and the metabolism of drugs, such as imatinib or fingolimod, and certain endog...
Article
Full-text available
Warfarin, an oral anticoagulant, has been used for decades to prevent thromboembolic events. The complex interplay between CYP2C9 and VKORC1 genotypes on warfarin PK and PD properties is not fully understood in special subgroups of patients. This study aimed to externally validate a population pharmacokinetic/pharma-codynamic (PK/PD) model for the...
Article
This study reports efforts toward the integrated advanced manufacturing of the anti-narcoleptic drug modafinil via flow chemistry and continuous crystallization.
Preprint
Full-text available
Clopidogrel, a prescription drug to reduce ischemic events in cardiovascular patients, has been extensively studied in mostly European individuals but not among Caribbean Hispanics. This study evaluated the low abundance and reduced activity of paraoxonase-1 (PON1) in clopidogrel-resistant patients as a predictive risk biomarker of poor responders...
Preprint
Full-text available
Background After percutaneous coronary intervention (PCI), clopidogrel resistant patients are at an increased risk of major adverse cardiovascular and cerebrovascular events (MACCEs). We aimed to assess whether genotype-guided selection of oral antiplatelet drugs using a clinical decision support (CDS) algorithm reduces the occurrence of these isch...
Preprint
Full-text available
Background High on-treatment platelet reactivity (HTPR) with clopidogrel is predictive of ischemic events in adults with coronary artery disease. Despite strong data suggesting HTPR varies with ethnicity, including clinical and genetic variables, no genome-wide association study (GWAS) of clopidogrel response has been performed among Caribbean Hisp...
Article
Full-text available
Cardiovascular disease (CVD) is one of the leading causes of death in Puerto Rico, where clopidogrel is commonly prescribed to prevent ischemic events. Genetic contributors to both a poor clopidogrel response and the severity of CVD have been identified mainly in Europeans. However, the non-random enrichment of single-nucleotide polymorphisms (SNPs...
Preprint
Full-text available
Cardiovascular disease (CVD) is one of the leading causes of death in Puerto Rico, where clopidogrel is commonly prescribed to prevent ischemic events. Genetic contributors to both a poor clopidogrel response and the severity of CVD have been identified mainly in Europeans. However, the non-random enrichment of single nucleotide polymorphisms (SNPs...
Article
Full-text available
We summarize some of the pathophysiological mechanisms of SARS-Cov2 infection, and address vulnerabilities related to healthy lifestyle habits (nutrition, supplementation, exercise, rest, and autonomic balance) on the optimization of the immune system and health. In addition we discuss post-vaccine injuries (adverse effects) and propose orthomolecu...
Article
A Vignette From Clinical Experience The mother of Bob, an 18-year-old student headed to college, calls the clinical laboratory requesting pharmacogenetics test results and the “traffic-light” drug guidance table from 12 years ago. As a boy, Bob had been treated by a child psychiatrist for autism spectrum disorder and anxiety. She was told these res...
Article
Full-text available
OBJECTIVES/GOALS: The purpose of this pilot study is to evaluate the clinical utility and patient/provider acceptability of a buprenorphine (bup) precision dosing approach for opioid use disorder (OUD) in Puerto Rico (PR) to in estimate the most adequate bup dosing regimen based on the unique pharmacological and clinical characteristics of these pa...
Article
Full-text available
A significant number of COVID-19 patients suffer from SARS-CoV-2 post-acute chronic sequelae, also known as post-COVID syndrome or long COVID. These patients report a broad range of persistent and debilitating symptoms such as fatigue, brain fog, pain, breathlessness, and dysrhythmias. These chronic symptoms are believed to be a consequence of exce...
Article
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Although supplements of essential nutrients can have therapeutic potential, they are qualitatively different from drugs. Many drugs are more toxic than micronutrients and have widespread and unique biological qualities. Failure to take into account the multiple functions of essential nutrients and how disease states can dramatically alter micronutr...
Article
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La investigación clínica in vitro e in vivo nos ha permitido comprender algunos de los mecanismos involucrados e incluso correlacionar las concentraciones con el efecto. Informes recientes sugieren que, incluso en países de altos ingresos como losEstados Unidos, una proporción considerable dela población tiene niveles inadecuados. Dada laprevalenci...
Article
Full-text available
Context: Pharmacokinetic studies play a fundamental role in making informed decisions during the drug development stage and fulfilling regulatory agencies’ requirements for drug approval. Disposition profiles of plasma drug concentrations over time can be characterized by using non-compartmental analysis, compartmental and physiological-based model...
Article
Accuracy of warfarin dose prediction algorithms may be improved by including data from diverse populations in genetic studies of dose variability. Here, we surveyed single nucleotide polymorphisms in vitamin K‐related genes for association with warfarin dose requirements in two admixed Latino populations in standard‐principal component adjusted and...
Article
Full-text available
Cancer accounts for nearly one-quarter of deaths in the United States. The life expectancy after standard treatment for these patients is dismal. New treatment modalities should be considered and evaluated. Ascorbic Acid (AA, Vitamin C) is a relatively low cost and safe nutrient even when given at very high doses (intravenous) that could be a very...
Article
Full-text available
OBJECTIVES/GOALS: To summarize baseline characteristics and risk factors for major adverse cardiovascular events (MACEs) and develop a prediction model by testing the association between genetic variants and MACEs in Caribbean Hispanic patients on clopidogrel using machine-learning (ML) techniques. METHODS/STUDY POPULATION: This is a secondary anal...
Article
Full-text available
Purpose Differences in the suppression of withdrawal symptoms have been observed in opioid-use-disorder (OUD) patients who were switched from Suboxone (the brand name of buprenorphine/naloxone sublingual films) to either 1 of 2 generic versions. These descriptive observations evidence the need to further assess the use of these generics and its imp...
Article
Modafinil is an anti-narcoleptic drug used to treat excessive daytime sleepiness associated with sleep apnea and shift-work disorder. It is unique in its lack of significant side-effects or addiction-inducing properties...
Article
Full-text available
A 56-year-old patient with a 1-year history of stable maintenance treatment with Suboxone for opioid use disorder (OUD) was switched to a generic formulation in May of 2019. The patient reported experiencing-over the course of the following 3 months-withdrawal symptoms when switched to the Alvogen-produced generic formulation in May of 2019 and the...
Article
Full-text available
Populations used to create warfarin dose prediction algorithms largely lacked participants reporting Hispanic or Latino ethnicity. While previous research suggests nonlinear modeling improves warfarin dose prediction, this research has mainly focused on populations with primarily European ancestry. We compare the accuracy of stable warfarin dose pr...
Article
Full-text available
Triple Negative Breast Cancer (TNBC) is an aggressive form of breast cancer, with a high predisposition for locally invasive and metastatic cancer. With the objective to reduce cancer metastasis, we developed small molecule inhibitors to target the drivers of metastasis, the Rho GTPases Rac and Cdc42. Of these, MBQ-167 inhibits both Rac and Cdc42 w...
Article
Full-text available
This multicenter clinical study was aimed at conducting a targeted pharmacogenomic association analysis of residual on‐clopidogrel platelet reactivity in 474 Caribbean Hispanic patients. Platelet reactivity was measured using the VerifyNow P2Y12 assay and clopidogrel resistance was defined as P2Y12 reaction units (PRUs) greater than or equal to 208...
Article
Full-text available
Vaccines represent preventative interventions amenable to immunogenetic prediction of how human variability will influence their safety and efficacy. The genetic polymorphism among individuals within any population can render possible that the immunity elicited by a vaccine is variable in length and strength. The same immune challenge (virus and/or...
Article
Full-text available
The Pharmacogene Variation Consortium (PharmVar) catalogues star (*) allele nomenclature for the polymorphic human CYP2C9 gene. Genetic variation within the CYP2C9 gene locus impacts the metabolism or bioactivation of many clinically important drugs including NSAIDs, phenytoin, anti‐diabetic agents and angiotensin receptor blocker. Variable CYP2C9...
Preprint
Full-text available
This article assesses the role of recipient genetics to COVID-19 vaccine responses. Vaccines represent preventative interventions suitable to an immunogenetic perspective to predict how human variability will influence their safety and efficacy. The genetic polymorphism among individuals within any population can make possible that the immunity eli...
Article
Full-text available
Non-Hispanic whites present with higher atrial fibrillation (AF) prevalence than other racial minorities living in the mainland USA. In two hospital-based studies, Puerto Rican Hispanics had a lower prevalence of atrial fibrillation of 2.5% than non-Hispanic Whites with 5.7%. This data is particularly controversial because Hispanics possess a highe...
Article
Full-text available
Context: Glutathione (GSH) is a major intracellular antioxidant capable of scavenging free radicals and detoxifying electrophiles from endogenous and exogenous sources via the free thiol group. GSH plays an important role in a multiple cellular process, including cell differentiation, proliferation, and apoptosis. Pharmacogenomics has demonstrated...
Article
Full-text available
Background: The aim of this analysis was to characterize the pharmacokinetics (PK) of sublingual buprenorphine (BUP) and its metabolites (buprenorphine glucuronide; BUP-g, norbuprenorphine; Nor-BUP, and norbuprenorphine glucuronide; Nor-BUP-g) in opioid use disorder (OUD) patients in Puerto Rico (PR) as a first step of evidence-based BUP dosing st...
Article
Full-text available
MBQ-167 is a dual inhibitor of the Rho GTPases Rac and Cdc42 that has shown promising results as an anti-cancer therapeutic at the preclinical stage. This drug has been tested in vitro and in vivo in metastatic breast cancer mouse models. The aim of this study is to develop a physiologically based pharmacokinetic/pharmacodynamic (PBPK-PD) model of...
Article
Full-text available
We conducted a multi‐site investigation of genetic determinants of warfarin dose variability in Latinos from the U.S. and Brazil. Patients from five institutions in the U.S. (n=411) and Brazil (n=663) were genotyped for VKORC1 c.‐1639G>A, common CYP2C9 variants, CYP4F2*3, and NQO1*2. Multiple regression analysis was used in the U.S. cohort to test...
Article
Objectives The inter-individual variability of warfarin dosing has been linked to genetic polymorphisms. This study was aimed at performing genotype-driven pharmacokinetic (PK) simulations to predict warfarin levels in Puerto Ricans. Methods Analysis of each individual dataset was performed by one-compartmental modeling using WinNonlin®v6.4. The k...
Article
Objectives: The inter-individual variability of warfarin dosing has been linked to genetic polymorphisms. This study was aimed at performing genotype-driven pharmacokinetic (PK) simulations to predict warfarin levels in Puerto Ricans. Methods: Analysis of each individual dataset was performed by one-compartmental modeling using WinNonlin®v6.4. T...
Conference Paper
The Rho GTPases Rac and Cdc42 are potential targets against metastatic disease. Our group characterized the small molecule MBQ-167 as an effective dual Rac/Cdc42 inhibitor that reduces HER2 positive and triple negative tumor growth and metastasis in mice by ~90%. To continue validating this drug for FDA approval, we recently elucidated the plasma p...
Article
Full-text available
Introduction Minority populations in the USA are disproportionately affected by cardiovascular conditions. Reduced responsiveness to clopidogrel among carriers of CYP2C19 variants has been reported in patients with either coronary artery disease (CAD) or acute coronary syndrome (ACS) after the percutaneous coronary intervention (PCI). Previous stud...
Article
Full-text available
As the opioid epidemic continues to grow across the United States, the number of patients requiring treatment for opioid use disorder continues to climb. Although medication-assisted treatment presents a highly effective tool that can help address this epidemic, its use has been limited. Nonetheless, with easier dosing protocols (compared to the mo...
Article
Full-text available
The new coronavirus (2019-nCoV) and its pulmonary and systemic complications have caused worldwide concern and emergency. There is a lack of effective targeted antiviral drugs and symptomatic supportive treatment. Ascorbic acid (AA) is an essential nutrient with important and diverse physiological effects that has demonstrated at high doses a varie...
Article
The Pharmacogene Variation Consortium (PharmVar) catalogues star (*) allele nomenclature for the polymorphic human CYP2C19 gene. CYP2C19 genetic variation impacts the metabolism of many drugs and has been associated with both, efficacy and safety issues for several commonly prescribed medications. This GeneFocus provides a comprehensive overview an...
Article
Full-text available
OBJECTIVES/GOALS: The use of P2Y12 receptor inhibitors like Clopidogrel is crucial in the prevention of thrombotic events in patients with coronary artery disease, peripheral arterial disease, and cerebrovascular disease. Variation in the level of platelet inhibition is present in many patients, and it is associated with the occurrence of major adv...
Article
Full-text available
Introduction: Pharmacists are poised to be the health care professionals best suited to provide medication-related consults and services based on a patient's genetics. Despite its potential benefits, the implementation of pharmacogenetic (PGx) testing into primary clinical settings has been slow among medically underserved populations. To our know...
Article
The resistance to clopidogrel increases the risk of ischemic events in adults with coronary artery disease. This resistance varies with ethnicity, genetic, and many other clinical variables. Proteomic data from studies on Caribbean Hispanic (CH) patients treated with clopidogrel that have developed resistance has not yet been conducted. Thus, this...
Chapter
Statin-associated muscle symptoms (SAMS) are a major cause of statin discontinuation. This chapter reviews the genomic basis of SAMS. Multiple genomic studies have identified various loci that seem to be associated with an increased risk of SAMS, but the statin-specific and phenotype-dependent association of simvastatin with SLCO1B1∗5 remains the m...
Article
Full-text available
Despite some previous examples of successful application to the field of pharmacogenomics, the utility of machine learning (ML) techniques for warfarin dose predictions in Caribbean Hispanic patients has yet to be fully evaluated. This study compares seven ML methods to predict warfarin dosing in Caribbean Hispanics. This is a secondary analysis of...
Article
Full-text available
Currently, there is no vaccine or specific antiviral medication for COVID-19. An accessible, effective and safe treatment is urgently needed to save lives and curtail the spreading of this disease. Acute respiratory distress syndrome (ARDS) is a key factor in the fatality outcome of COVID-19. Significantly increased oxidative stress due to rapid re...
Article
Warfarin is the most commonly used oral anticoagulant in sub-Saharan Africa. Dosing is challenging due to a narrow therapeutic index and high inter-individual variability in dose requirements. To evaluate the genetic factors affecting warfarin dosing in Black-Africans, we performed a meta-analysis of 48 studies (2,336 patients). Significant predict...
Article
Full-text available
The Rho GTPases Rac and Cdc42 are potential targets against metastatic diseases. We characterized the small molecule MBQ-167 as an effective dual Rac/Cdc42 inhibitor that reduces HER2-type tumor growth and metastasis in mice by ∼90%. This study reports the pharmacokinetics and tissue distribution of MBQ-167 following intraperitoneal and oral single...
Article
Full-text available
Aim: Perform in silico predictions of functional consequences of CYP2C9 variants identified by next-generation sequencing in Puerto Ricans. Methods: Identified low-frequency CYP2C9 variants (minor allele frequencies <2%) were evaluated using the Combined Annotation-Dependent Depletion (CADD v1.3) tools and molecular modeling/docking analysis to pre...
Article
Aim: Variants of the MTHFR gene have been associated with a wide range of diseases. Materials & methods: The present study analyzed data from clinical genotyping of MTHFR 677C>T and 1298A>C in 1405 patients in urban primary care settings. Results: Striking differences in ethnogeographic frequencies of MTHFR polymorphisms were observed. African-Amer...
Article
The solubility of warfarin sodium isopropanol solvate (WS·IPA), a widely used anticoagulant, was determined at temperatures ranging from 278.15 to 333.15 K in four pure solvents (acetone, ethanol, IPA, and water), five binary solvent mixtures (IPA + acetone, IPA + ethanol, IPA + water, IPA + heptane, and IPA + hexane), and five ternary solvent mixt...
Article
Full-text available
OBJECTIVES/SPECIFIC AIMS: Consequently, we have decided to evaluate the presence of single nucleotide polymorphism (SNP) previously associated with AF on a European-descent population in an attempt to first identify the most common loci present in the PRH population and then search for specific PRH SNP associated with AF. METHODS/STUDY POPULATION:...
Article
Full-text available
Purpose: Although clopidogrel is the most widely used oral P2Y12 receptor antagonist, up to 10% of acute coronary syndrome patients treated with clopidogrel will experience a recurrent myocardial infarction and 2-3% will experience stent thrombosis within 1 year. The purpose of this research is to describe the prevalence of pharmacogene variants a...
Article
Full-text available
Warfarin continues to be the mainstay therapy for preventing thrombus formation. Although pharmacogenetic algorithms have shown higher predictability of the optimal warfarin dose and lower occurrence of bleeding episodes, they often do not include ethno-specific genetic variants relevant to non-Europeans. This case report describes a rare missense...
Article
Full-text available
Abstract Background: Vitamin C has been useful in the treatment of anemia due to chronic illness but not utilized frequently in clinical practice. Regarding Vitamin E, small human and animal studies have shown benefits. The available evidence with regards to the benefits of high dose Intravenous Vitamin C (IVC) and oral vitamin E in anemia in chron...
Article
Metastasis is the principal cause of death for most cancer patients; however, effective treatment options are limited. The Rho GTPases Rac and Cdc42 are critical regulators of cancer cell migration and invasion; processes required for metastatic progression. Hence, targeting of these pivotal regulators is a rational approach for novel metastasis fo...
Article
Full-text available
Introduction High on-treatment platelet reactivity (HTPR) to clopidogrel imparts an increased risk for ischemic events in adults with coronary artery disease. Platelet reactivity varies with ethnicity and is influenced by both clinical and genetic variables; however, no clopidogrel pharmacogenetic studies with Puerto Rican patients have been report...
Data
Supplementary Materials: The following are available online at http://www.mdpi.com/1660-4601/15/6/1115/s1. Table S1: Genotype and allelic frequencies of seven relevant polymorphisms occurring on four pharmacogenes of interest (i.e., potentially to be associated with Clopidogrel response) in the Puerto Rican population. Data correspond to genomic DN...
Article
Full-text available
OBJECTIVES/SPECIFIC AIMS: High on-treatment platelet reactivity (HTPR) with clopidogrel imparts an increased risk for ischemic events in adults with coronary artery disease. Although more potent antiplatelet agents are available, clopidogrel remains the most commonly used P2Y12 inhibitor in Puerto Rico. Platelet reactivity varies with ethnicity and...
Article
Full-text available
Background: Variations in several clopidogrel-pharmacogenes have been linked to clopidogrel response variability and clinical outcomes. We aimed to determine the frequency distribution of major polymorphisms on CYP2C19, PON1, ABCB1 and P2RY12 pharmacogenes in Puerto Ricans. Methods: This was a cross-sectional, population-based study of 200 unrelate...
Preprint
Full-text available
Background: Variations in several clopidogrel-pharmacogenes have been linked to clopidogrel response variability and clinical outcomes. We aimed to determine the frequency distribution of major polymorphisms on CYP2C19, PON1, ABCB1 and P2RY12 pharmacogenes in Puerto Ricans. Methods: This was a cross-sectional, population-based study of 200 unrelate...