Niels Westergaard, Trine Meldgaard Lund, Charlotte Vermehren
Precision medicine has significantly advanced through the development of predictive biomarkers based on pharmacogenetic (PGx) testing. These tests identify interactions between drugs and genetic variants that influence patient responses to treatments. Understanding genetic variations in drug-metabolizing enzymes, receptors and transporters and their impact on pharmacokinetics and pharmacodynamics allows for the prediction of drug effects and side effects, enabling tailored treatments for different patient groups. This review focuses on drugs metabolized by cytochrome P450 (CYP450) enzymes, for example, citalopram and clopidogrel or transported by the solute carrier organic anion transporter family member 1B1 (SLCO1B1), for example, atorvastatin and simvastatin, with PGx dosing guidelines, in the context of consumption in Scandinavian countries. A major barrier to the widespread adoption of PGx tests in clinical practice has been healthcare professionals' uncertainty about their efficacy, complexity in result interpretation and questions regarding the evidence base. However, recent studies have demonstrated PGx testing has the potential to improve treatment outcomes, reduce adverse drug reactions and achieve cost savings. These findings underscore the potential of PGx testing as a valuable tool in clinical decision making, promoting its use in a pre-emptive manner to enhance patient care.
{"title":"Predictive Biomarkers and Personalized Therapy: Use of Pharmacogenetic Testing in a Scandinavian Perspective","authors":"Niels Westergaard, Trine Meldgaard Lund, Charlotte Vermehren","doi":"10.1111/bcpt.70009","DOIUrl":"https://doi.org/10.1111/bcpt.70009","url":null,"abstract":"<p>Precision medicine has significantly advanced through the development of predictive biomarkers based on pharmacogenetic (PGx) testing. These tests identify interactions between drugs and genetic variants that influence patient responses to treatments. Understanding genetic variations in drug-metabolizing enzymes, receptors and transporters and their impact on pharmacokinetics and pharmacodynamics allows for the prediction of drug effects and side effects, enabling tailored treatments for different patient groups. This review focuses on drugs metabolized by cytochrome P450 (CYP450) enzymes, for example, citalopram and clopidogrel or transported by the solute carrier organic anion transporter family member 1B1 (SLCO1B1), for example, atorvastatin and simvastatin, with PGx dosing guidelines, in the context of consumption in Scandinavian countries. A major barrier to the widespread adoption of PGx tests in clinical practice has been healthcare professionals' uncertainty about their efficacy, complexity in result interpretation and questions regarding the evidence base. However, recent studies have demonstrated PGx testing has the potential to improve treatment outcomes, reduce adverse drug reactions and achieve cost savings. These findings underscore the potential of PGx testing as a valuable tool in clinical decision making, promoting its use in a pre-emptive manner to enhance patient care.</p>","PeriodicalId":8733,"journal":{"name":"Basic & Clinical Pharmacology & Toxicology","volume":"136 3","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bcpt.70009","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143446814","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Elijah Oluwatosin Olopade, Stephen Adeniyi Adefegha, Jude Oluwapelumi Alao, Ayodeji Emmanuel Adepoju, Aderonke Elizabeth Fakayode, Ganiyu Oboh
Male sexual dysfunction, characterised by reduced libido, ejaculatory issues and erectile dysfunction, often results from oxidative stress and enzymatic imbalance, notably involving phosphodiesterase type 5 (PDE5) and nitric oxide synthase (NOS). This study explores the therapeutic potential of β-caryophyllene (β-CBP), a sesquiterpene with antioxidant and anti-inflammatory properties, in mitigating paroxetine-induced sexual dysfunction in rats. Male Wistar rats were divided into nine treatment groups: control, paroxetine (20 mg/kg/day), sildenafil (20 mg/kg/day), β-CBP (10 mg/kg/day), β-CBP (20 mg/kg/day), paroxetine with β-CBP (10 mg/kg), paroxetine with β-CBP (20 mg/kg), paroxetine with sildenafil and β-CBP with sildenafil. Sexual behavioural assays were evaluated, along with oxidative stress markers, including superoxide dismutase (SOD) and catalase (CAT) activity in penile tissue, assessed using spectrophotometric analysis. CB2 receptor expression was significantly increased in β-CBP-treated groups, suggesting enhanced cannabinoid receptor-mediated signalling, which may be linked to improved erectile function. The effects were dose-dependent, with the 20 mg/kg β-CBP group displaying the most significant improvements. Additionally, β-CBP restored antioxidant enzyme activities, including SOD, CAT and reduced glutathione (GSH) levels in penile tissue, effectively reducing oxidative stress. β-CBP shows promise as a therapeutic agent for male sexual dysfunction by enhancing antioxidative capacity and modulating enzymatic balance.
{"title":"Ameliorative Role of β-Caryophyllene on Antioxidant Biomarkers in a Paroxetine-Induced Model of Male Sexual Dysfunction","authors":"Elijah Oluwatosin Olopade, Stephen Adeniyi Adefegha, Jude Oluwapelumi Alao, Ayodeji Emmanuel Adepoju, Aderonke Elizabeth Fakayode, Ganiyu Oboh","doi":"10.1111/bcpt.70010","DOIUrl":"https://doi.org/10.1111/bcpt.70010","url":null,"abstract":"<p>Male sexual dysfunction, characterised by reduced libido, ejaculatory issues and erectile dysfunction, often results from oxidative stress and enzymatic imbalance, notably involving phosphodiesterase type 5 (PDE5) and nitric oxide synthase (NOS). This study explores the therapeutic potential of β-caryophyllene (β-CBP), a sesquiterpene with antioxidant and anti-inflammatory properties, in mitigating paroxetine-induced sexual dysfunction in rats. Male Wistar rats were divided into nine treatment groups: control, paroxetine (20 mg/kg/day), sildenafil (20 mg/kg/day), β-CBP (10 mg/kg/day), β-CBP (20 mg/kg/day), paroxetine with β-CBP (10 mg/kg), paroxetine with β-CBP (20 mg/kg), paroxetine with sildenafil and β-CBP with sildenafil. Sexual behavioural assays were evaluated, along with oxidative stress markers, including superoxide dismutase (SOD) and catalase (CAT) activity in penile tissue, assessed using spectrophotometric analysis. CB2 receptor expression was significantly increased in β-CBP-treated groups, suggesting enhanced cannabinoid receptor-mediated signalling, which may be linked to improved erectile function. The effects were dose-dependent, with the 20 mg/kg β-CBP group displaying the most significant improvements. Additionally, β-CBP restored antioxidant enzyme activities, including SOD, CAT and reduced glutathione (GSH) levels in penile tissue, effectively reducing oxidative stress. β-CBP shows promise as a therapeutic agent for male sexual dysfunction by enhancing antioxidative capacity and modulating enzymatic balance.</p>","PeriodicalId":8733,"journal":{"name":"Basic & Clinical Pharmacology & Toxicology","volume":"136 3","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bcpt.70010","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143424071","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Correction to “The Protective Effect of Modafinil on Vincristine-Induced Peripheral Neuropathy in Rats: A Possible Role for TRPA1 Receptors”","authors":"","doi":"10.1111/bcpt.70006","DOIUrl":"https://doi.org/10.1111/bcpt.70006","url":null,"abstract":"<p>We apologize for the adjustments.</p><p>We apologize.</p>","PeriodicalId":8733,"journal":{"name":"Basic & Clinical Pharmacology & Toxicology","volume":"136 3","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-02-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bcpt.70006","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143424000","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}