Pub Date : 2022-06-01Epub Date: 2022-08-05DOI: 10.1080/17425255.2022.2106214
Georgios Schoretsanitis, Kristina M Deligiannidis, Michael Paulzen, Edoardo Spina, Jose de Leon
Introduction: This is a comprehensive overview of pharmacokinetic drug-drug interactions (DDIs) involving oral contraceptives (OCs) and psychotropic medications.
Areas covered: Medline and Embase from inception to April 2021 were searched for DDIs between OCs and psychotropic medications. They included case reports/series and cross-sectional, cross-over, placebo-controlled studies of patient cohorts and healthy females. We classified DDIs as: combined hormonal contraceptives (CHCs) acting as victim drugs (i.e. affected by psychotropic co-medications), CHCs as perpetrators, (i.e. affecting the activity of psychotropic co-medications), progestin-derivatives as victim drugs and progestin-derivatives affecting psychotropic co-medications. Alteration ratios reflecting changes in pharmacokinetic parameters before and after the DDI were estimated to approximate the extent of the DDI.
Expert opinion: Women taking antiepileptic agents with strong to moderate enzyme-inducing properties (carbamazepine, phenobarbital, phenytoin) or those with moderate to mild enzyme-inducing properties (cenobamate, clobazam, eslicarbazepine, felbamate, oxcarbazepine, rufinamide, topiramate) should avoid OCs. Daily doses of cytochrome P450 1A2 substrates including clozapine may need to be reduced by 50% in women taking concomitant CHCs. Compared to CHCs, the propensity of progestin-only pills for DDIs has been investigated less. We provide a summary table for clinicians containing recommendations based on literature and package inserts; whenever evidence was available, we provided dose-correction factors.
{"title":"Drug-drug interactions between psychotropic medications and oral contraceptives.","authors":"Georgios Schoretsanitis, Kristina M Deligiannidis, Michael Paulzen, Edoardo Spina, Jose de Leon","doi":"10.1080/17425255.2022.2106214","DOIUrl":"https://doi.org/10.1080/17425255.2022.2106214","url":null,"abstract":"<p><strong>Introduction: </strong>This is a comprehensive overview of pharmacokinetic drug-drug interactions (DDIs) involving oral contraceptives (OCs) and psychotropic medications.</p><p><strong>Areas covered: </strong>Medline and Embase from inception to April 2021 were searched for DDIs between OCs and psychotropic medications. They included case reports/series and cross-sectional, cross-over, placebo-controlled studies of patient cohorts and healthy females. We classified DDIs as: combined hormonal contraceptives (CHCs) acting as victim drugs (i.e. affected by psychotropic co-medications), CHCs as perpetrators, (i.e. affecting the activity of psychotropic co-medications), progestin-derivatives as victim drugs and progestin-derivatives affecting psychotropic co-medications. Alteration ratios reflecting changes in pharmacokinetic parameters before and after the DDI were estimated to approximate the extent of the DDI.</p><p><strong>Expert opinion: </strong>Women taking antiepileptic agents with strong to moderate enzyme-inducing properties (carbamazepine, phenobarbital, phenytoin) or those with moderate to mild enzyme-inducing properties (cenobamate, clobazam, eslicarbazepine, felbamate, oxcarbazepine, rufinamide, topiramate) should avoid OCs. Daily doses of cytochrome P450 1A2 substrates including clozapine may need to be reduced by 50% in women taking concomitant CHCs. Compared to CHCs, the propensity of progestin-only pills for DDIs has been investigated less. We provide a summary table for clinicians containing recommendations based on literature and package inserts; whenever evidence was available, we provided dose-correction factors.</p>","PeriodicalId":12250,"journal":{"name":"Expert Opinion on Drug Metabolism & Toxicology","volume":"18 6","pages":"395-411"},"PeriodicalIF":4.3,"publicationDate":"2022-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40646333","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-05-01Epub Date: 2022-07-17DOI: 10.1080/17425255.2022.2098106
Sherilyn Wong, Stephanie E Reuter, Graham Rd Jones, Sophie L Stocker
Introduction: Vancomycin dosing decisions are informed by factors such as body weight and renal function. It is important to understand the impact of obesity on vancomycin pharmacokinetics and how this may influence dosing decisions. Vancomycin dosing guidelines use varied descriptors of body weight and renal function. There is uncertainty whether current dosing guidelines result in attainment of therapeutic targets in obese individuals.
Areas covered: Literature was explored using PubMed, Embase, and Google Scholar for articles from January 1980 to July 2021 regarding obesity-driven physiological changes, their influence on vancomycin pharmacokinetics and body size descriptors and renal function calculations in vancomycin dosing. Pharmacokinetic simulations reflective of international vancomycin dosing guidelines were conducted to evaluate the ability of using total, ideal, and adjusted body weight, as well as Cockcroft-Gault and CKD-EPI equations to attain an area-under-the-curve to minimum inhibitory concentration ratio (AUC24/MIC) target (400-650) in obese individuals.
Expert opinion: Vancomycin pharmacokinetics in obese individuals remains debated. Guidelines that determine loading doses using total body weight, and maintenance doses adjusted based on renal function and adjusted body weight, may be most appropriate for obese individuals. Use of ideal body weight leads to subtherapeutic vancomycin exposure and underestimation of renal function.
{"title":"Review and evaluation of vancomycin dosing guidelines for obese individuals.","authors":"Sherilyn Wong, Stephanie E Reuter, Graham Rd Jones, Sophie L Stocker","doi":"10.1080/17425255.2022.2098106","DOIUrl":"https://doi.org/10.1080/17425255.2022.2098106","url":null,"abstract":"<p><strong>Introduction: </strong>Vancomycin dosing decisions are informed by factors such as body weight and renal function. It is important to understand the impact of obesity on vancomycin pharmacokinetics and how this may influence dosing decisions. Vancomycin dosing guidelines use varied descriptors of body weight and renal function. There is uncertainty whether current dosing guidelines result in attainment of therapeutic targets in obese individuals.</p><p><strong>Areas covered: </strong>Literature was explored using PubMed, Embase, and Google Scholar for articles from January 1980 to July 2021 regarding obesity-driven physiological changes, their influence on vancomycin pharmacokinetics and body size descriptors and renal function calculations in vancomycin dosing. Pharmacokinetic simulations reflective of international vancomycin dosing guidelines were conducted to evaluate the ability of using total, ideal, and adjusted body weight, as well as Cockcroft-Gault and CKD-EPI equations to attain an area-under-the-curve to minimum inhibitory concentration ratio (AUC<sub>24</sub>/MIC) target (400-650) in obese individuals.</p><p><strong>Expert opinion: </strong>Vancomycin pharmacokinetics in obese individuals remains debated. Guidelines that determine loading doses using total body weight, and maintenance doses adjusted based on renal function and adjusted body weight, may be most appropriate for obese individuals. Use of ideal body weight leads to subtherapeutic vancomycin exposure and underestimation of renal function.</p>","PeriodicalId":12250,"journal":{"name":"Expert Opinion on Drug Metabolism & Toxicology","volume":"18 5","pages":"323-335"},"PeriodicalIF":4.3,"publicationDate":"2022-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40582808","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-05-01Epub Date: 2022-07-12DOI: 10.1080/17425255.2022.2099835
Laura Calabrese, Andrea Chiricozzi, Clara De Simone, Barbara Fossati, Alessandra D'Amore, Ketty Peris
Introduction: Atopic dermatitis (AD) is the most common inflammatory skin disorder. Despite the high disease burden, the therapeutic options are limited and their efficacy in controlling AD might be partially satisfactory.
Areas covered: Most of the key mediators in AD pathogenesis act through the JAK/STAT signaling pathway, which represents a valid therapeutic target. The first generation of JAK inhibitors, namely tofacitinib and ruxolitinib, inhibit multiple JAKs, whereas newer JAK inhibitors show more selective inhibitory effects for specific JAKs. The aim of this review was to discuss the role of the JAK/STAT pathway in AD and its inhibition, with a special focus on pharmacodynamic properties.
Expert opinion: JAK inhibitors have different selectivity for various JAK molecules, which influences their pharmacodynamics, efficacy, and safety profile. Since many key cytokines in AD signal through JAK1, the selective JAK1 inhibition may be effective, avoiding the concomitant inhibition of JAK2- and JAK3-dependent pathways could be associated with additional safety issues. Therefore, selective JAK1 inhibitors may represent promising therapeutic agents for AD, as they might prevent off-target effects of JAK inhibitors, especially related to the hematologic profile.
{"title":"Pharmacodynamics of Janus kinase inhibitors for the treatment of atopic dermatitis.","authors":"Laura Calabrese, Andrea Chiricozzi, Clara De Simone, Barbara Fossati, Alessandra D'Amore, Ketty Peris","doi":"10.1080/17425255.2022.2099835","DOIUrl":"https://doi.org/10.1080/17425255.2022.2099835","url":null,"abstract":"<p><strong>Introduction: </strong>Atopic dermatitis (AD) is the most common inflammatory skin disorder. Despite the high disease burden, the therapeutic options are limited and their efficacy in controlling AD might be partially satisfactory.</p><p><strong>Areas covered: </strong>Most of the key mediators in AD pathogenesis act through the JAK/STAT signaling pathway, which represents a valid therapeutic target. The first generation of JAK inhibitors, namely tofacitinib and ruxolitinib, inhibit multiple JAKs, whereas newer JAK inhibitors show more selective inhibitory effects for specific JAKs. The aim of this review was to discuss the role of the JAK/STAT pathway in AD and its inhibition, with a special focus on pharmacodynamic properties.</p><p><strong>Expert opinion: </strong>JAK inhibitors have different selectivity for various JAK molecules, which influences their pharmacodynamics, efficacy, and safety profile. Since many key cytokines in AD signal through JAK1, the selective JAK1 inhibition may be effective, avoiding the concomitant inhibition of JAK2- and JAK3-dependent pathways could be associated with additional safety issues. Therefore, selective JAK1 inhibitors may represent promising therapeutic agents for AD, as they might prevent off-target effects of JAK inhibitors, especially related to the hematologic profile.</p>","PeriodicalId":12250,"journal":{"name":"Expert Opinion on Drug Metabolism & Toxicology","volume":"18 5","pages":"347-355"},"PeriodicalIF":4.3,"publicationDate":"2022-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40566596","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-05-01Epub Date: 2022-07-18DOI: 10.1080/17425255.2022.2099837
Ayala Bar-Hai, Abraham J Domb, Amnon Hoffman
Introduction: Oral administration of cannabinoids is a convenient route of administration in many cases. To enhance the poor and variable bioavailability of cannabinoids, selected strategies utilizing proper delivery systems have been designed. Low solubility in the GI aqueous media is the first and most critical barrier. Thereafter, cannabinoids can reach the systemic blood circulation via the portal vein that is associated with significant hepatic first pass metabolism (FPM) or bypass it via lymphatic absorption.
Areas covered: The solubility obstacle of cannabinoids is mainly addressed with lipid-based formulations such as self-nanoemulsifying drug delivery systems (SNEDDS). Certain lipids are used to overcome the solubility issue. Surfactants and other additives in the formulation have additional impact on several barriers, including dictating the degree of lymphatic bioavailability and hepatic FPM. Gastro-retentive formulation is also plausible.
Expert opinion: Comparison of the role of the same SNEDDS formulation, cyclosporine vs. cannabinoids, when used to elevate the oral bioavailability of different compounds, is presented. It illustrates some similarities and major mechanistic differences obtained by the same SNEDDS. Thus, the different influence over the absorption pathway illuminates the importance of understanding the absorption mechanism and its barriers to properly select appropriate strategies to achieve enhanced oral bioavailability.
{"title":"Strategies for enhancing the oral bioavailability of cannabinoids.","authors":"Ayala Bar-Hai, Abraham J Domb, Amnon Hoffman","doi":"10.1080/17425255.2022.2099837","DOIUrl":"https://doi.org/10.1080/17425255.2022.2099837","url":null,"abstract":"<p><strong>Introduction: </strong>Oral administration of cannabinoids is a convenient route of administration in many cases. To enhance the poor and variable bioavailability of cannabinoids, selected strategies utilizing proper delivery systems have been designed. Low solubility in the GI aqueous media is the first and most critical barrier. Thereafter, cannabinoids can reach the systemic blood circulation via the portal vein that is associated with significant hepatic first pass metabolism (FPM) or bypass it via lymphatic absorption.</p><p><strong>Areas covered: </strong>The solubility obstacle of cannabinoids is mainly addressed with lipid-based formulations such as self-nanoemulsifying drug delivery systems (SNEDDS). Certain lipids are used to overcome the solubility issue. Surfactants and other additives in the formulation have additional impact on several barriers, including dictating the degree of lymphatic bioavailability and hepatic FPM. Gastro-retentive formulation is also plausible.</p><p><strong>Expert opinion: </strong>Comparison of the role of the same SNEDDS formulation, cyclosporine vs. cannabinoids, when used to elevate the oral bioavailability of different compounds, is presented. It illustrates some similarities and major mechanistic differences obtained by the same SNEDDS. Thus, the different influence over the absorption pathway illuminates the importance of understanding the absorption mechanism and its barriers to properly select appropriate strategies to achieve enhanced oral bioavailability.</p>","PeriodicalId":12250,"journal":{"name":"Expert Opinion on Drug Metabolism & Toxicology","volume":"18 5","pages":"313-322"},"PeriodicalIF":4.3,"publicationDate":"2022-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40608371","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-05-01Epub Date: 2022-07-11DOI: 10.1080/17425255.2022.2098107
Inès Ben Ghezala, Maxime Luu, Marc Bardou
Introduction: Proton pump inhibitors (PPIs) block the gastric H/K-ATPase, therefore inhibiting acid gastric secretion, leading to an increased pH (>4). They account for an extremely high number of prescriptions worldwide. Numerous drug-drug interactions have been described with PPIs, but all the described interactions do not have clinical significance.
Areas covered: This review will discuss the latest updates on drug-drug interactions with PPIs, focusing on the last 10-year publications in the following areas: anti-infective agents, anticancer drugs, antiplatelet agents and anticoagulants, and antidiabetics.
Expert opinion: Although pharmacokinetic interactions of PPIs have been described with many drugs, their clinical relevance remains controversial. However, given the extremely high number of people being treated with PPIs, clinicians should remain vigilant for interactions that may be clinically significant and require dose adjustment or therapeutic monitoring. Interestingly, not all PPIs have the same pharmacokinetic and pharmacodynamic profile, with some having a strong potential to inhibit CYP2C19, such as omeprazole, esomeprazole, and lansoprazole, while others, pantoprazole, rabeprazole, and dexlansoprazole, are weak CYP2C19 inhibitors. These may be preferred depending on co-prescribed treatments.In addition, new formulations have been developed to prevent some of the gastric pH-dependent drug interactions and should be evaluated in further large-scale prospective comparative studies.
质子泵抑制剂(PPIs)阻断胃H/ k - atp酶,从而抑制胃酸分泌,导致pH升高(>4)。它们在世界范围内的处方数量极高。许多药物-药物相互作用已被描述与PPIs,但所有描述的相互作用不具有临床意义。涵盖领域:本综述将讨论PPIs药物-药物相互作用的最新进展,重点关注过去10年在以下领域的出版物:抗感染药物、抗癌药物、抗血小板药物和抗凝血剂以及抗糖尿病药物。专家意见:尽管PPIs与许多药物的药代动力学相互作用已被描述,但其临床相关性仍存在争议。然而,鉴于接受质子泵抑制剂治疗的人数非常多,临床医生应该对可能具有临床意义的相互作用保持警惕,并需要调整剂量或进行治疗监测。有趣的是,并不是所有的PPIs都具有相同的药代动力学和药效学特征,一些PPIs具有很强的抑制CYP2C19的潜力,如奥美拉唑、埃索美拉唑和兰索拉唑,而其他PPIs,如泮托拉唑、雷贝拉唑和右兰索拉唑,是弱CYP2C19抑制剂。根据共同规定的治疗方法,这些可能是首选。此外,已经开发了新的配方来防止一些胃ph依赖性药物相互作用,应该在进一步的大规模前瞻性比较研究中进行评估。
{"title":"An update on drug-drug interactions associated with proton pump inhibitors.","authors":"Inès Ben Ghezala, Maxime Luu, Marc Bardou","doi":"10.1080/17425255.2022.2098107","DOIUrl":"https://doi.org/10.1080/17425255.2022.2098107","url":null,"abstract":"<p><strong>Introduction: </strong>Proton pump inhibitors (PPIs) block the gastric H/K-ATPase, therefore inhibiting acid gastric secretion, leading to an increased pH (>4). They account for an extremely high number of prescriptions worldwide. Numerous drug-drug interactions have been described with PPIs, but all the described interactions do not have clinical significance.</p><p><strong>Areas covered: </strong>This review will discuss the latest updates on drug-drug interactions with PPIs, focusing on the last 10-year publications in the following areas: anti-infective agents, anticancer drugs, antiplatelet agents and anticoagulants, and antidiabetics.</p><p><strong>Expert opinion: </strong>Although pharmacokinetic interactions of PPIs have been described with many drugs, their clinical relevance remains controversial. However, given the extremely high number of people being treated with PPIs, clinicians should remain vigilant for interactions that may be clinically significant and require dose adjustment or therapeutic monitoring. Interestingly, not all PPIs have the same pharmacokinetic and pharmacodynamic profile, with some having a strong potential to inhibit CYP2C19, such as omeprazole, esomeprazole, and lansoprazole, while others, pantoprazole, rabeprazole, and dexlansoprazole, are weak CYP2C19 inhibitors. These may be preferred depending on co-prescribed treatments.In addition, new formulations have been developed to prevent some of the gastric pH-dependent drug interactions and should be evaluated in further large-scale prospective comparative studies.</p>","PeriodicalId":12250,"journal":{"name":"Expert Opinion on Drug Metabolism & Toxicology","volume":"18 5","pages":"337-346"},"PeriodicalIF":4.3,"publicationDate":"2022-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40471841","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-05-01Epub Date: 2022-07-15DOI: 10.1080/17425255.2022.2099836
Karel Allegaert, Mohammad Yaseen Abbasi, Pieter Annaert, Olusola Olafuyi
Introduction: There is a need for structured approaches to inform on pharmacotherapy in preterm neonates. With their proven track record up to regulatory acceptance, physiologically based pharmacokinetic (PBPK) modeling and simulation provide a structured approach, and hold the promise to support drug development in preterm neonates.
Areas covered: Compared to general and pediatric use of PBPK modeling, its use to inform pharmacotherapy in preterms is limited. Using a systematic search (PBPK + preterm), we retained 25 records (20 research papers, 2 letters, 3 abstracts). We subsequently collated the published information on PBPK software packages (PK-Sim®, Simcyp®), and their applications and optimization efforts in preterm neonates. It is encouraging that applications cover a broad range of scenarios (pharmacokinetic-dynamic analyses, drug-drug interactions, developmental pharmacogenetics, lactation related exposure) and compounds (small molecules, proteins). Furthermore, specific compartments (cerebrospinal fluid, tissue) or (patho)physiologic processes (cardiac output, biliary excretion, first pass metabolism) are considered.
Expert opinion: Knowledge gaps exist, giving rise to various levels of uncertainty in PBPK applications in preterm neonates. To improve this, we need cross talk between clinicians and modelers to generate and integrate knowledge (PK datasets, system knowledge, maturational physiology and pathophysiology) to further refine PBPK models.
{"title":"Current and future physiologically based pharmacokinetic (PBPK) modeling approaches to optimize pharmacotherapy in preterm neonates.","authors":"Karel Allegaert, Mohammad Yaseen Abbasi, Pieter Annaert, Olusola Olafuyi","doi":"10.1080/17425255.2022.2099836","DOIUrl":"https://doi.org/10.1080/17425255.2022.2099836","url":null,"abstract":"<p><strong>Introduction: </strong>There is a need for structured approaches to inform on pharmacotherapy in preterm neonates. With their proven track record up to regulatory acceptance, physiologically based pharmacokinetic (PBPK) modeling and simulation provide a structured approach, and hold the promise to support drug development in preterm neonates.</p><p><strong>Areas covered: </strong>Compared to general and pediatric use of PBPK modeling, its use to inform pharmacotherapy in preterms is limited. Using a systematic search (PBPK + preterm), we retained 25 records (20 research papers, 2 letters, 3 abstracts). We subsequently collated the published information on PBPK software packages (PK-Sim®, Simcyp®), and their applications and optimization efforts in preterm neonates. It is encouraging that applications cover a broad range of scenarios (pharmacokinetic-dynamic analyses, drug-drug interactions, developmental pharmacogenetics, lactation related exposure) and compounds (small molecules, proteins). Furthermore, specific compartments (cerebrospinal fluid, tissue) or (patho)physiologic processes (cardiac output, biliary excretion, first pass metabolism) are considered.</p><p><strong>Expert opinion: </strong>Knowledge gaps exist, giving rise to various levels of uncertainty in PBPK applications in preterm neonates. To improve this, we need cross talk between clinicians and modelers to generate and integrate knowledge (PK datasets, system knowledge, maturational physiology and pathophysiology) to further refine PBPK models.</p>","PeriodicalId":12250,"journal":{"name":"Expert Opinion on Drug Metabolism & Toxicology","volume":"18 5","pages":"301-312"},"PeriodicalIF":4.3,"publicationDate":"2022-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40569030","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-04-03DOI: 10.1080/17425255.2022.2085552
P. Ballester, Javier Muriel, A. Peiró
ABSTRACT Introduction Opioids play a fundamental role in chronic pain, especially considering when 1 of 5 Europeans adults, even more in older females, suffer from it. However, half of them do not reach an adequate pain relief. Could pharmacogenomics help to choose the most appropriate analgesic drug? Areas covered The objective of the present narrative review was to assess the influence of cytochrome P450 2D6 (CYP2D6) phenotypes on pain relief, analgesic tolerability, and potential opioid misuse. Until December 2021, a literature search was conducted through the MEDLINE, PubMed database, including papers from the last 10 years. CYP2D6 plays a major role in metabolism that directly impacts on opioid (tramadol, codeine, or oxycodone) concentration with differences between sexes, with a female trend toward poorer pain control. In fact, CYP2D6 gene variants are the most actionable to be translated into clinical practice according to regulatory drug agencies and international guidelines. Expert Opinion CYP2D6 genotype can influence opioids’ pharmacokinetics, effectiveness, side effects, and average opioid dose. This knowledge needs to be incorporated in pain management. Environmental factors, psychological together with genetic factors, under a sex perspective, must be considered when you are selecting the most personalized pain therapy for your patients.
{"title":"CYP2D6 phenotypes and opioid metabolism: the path to personalized analgesia","authors":"P. Ballester, Javier Muriel, A. Peiró","doi":"10.1080/17425255.2022.2085552","DOIUrl":"https://doi.org/10.1080/17425255.2022.2085552","url":null,"abstract":"ABSTRACT Introduction Opioids play a fundamental role in chronic pain, especially considering when 1 of 5 Europeans adults, even more in older females, suffer from it. However, half of them do not reach an adequate pain relief. Could pharmacogenomics help to choose the most appropriate analgesic drug? Areas covered The objective of the present narrative review was to assess the influence of cytochrome P450 2D6 (CYP2D6) phenotypes on pain relief, analgesic tolerability, and potential opioid misuse. Until December 2021, a literature search was conducted through the MEDLINE, PubMed database, including papers from the last 10 years. CYP2D6 plays a major role in metabolism that directly impacts on opioid (tramadol, codeine, or oxycodone) concentration with differences between sexes, with a female trend toward poorer pain control. In fact, CYP2D6 gene variants are the most actionable to be translated into clinical practice according to regulatory drug agencies and international guidelines. Expert Opinion CYP2D6 genotype can influence opioids’ pharmacokinetics, effectiveness, side effects, and average opioid dose. This knowledge needs to be incorporated in pain management. Environmental factors, psychological together with genetic factors, under a sex perspective, must be considered when you are selecting the most personalized pain therapy for your patients.","PeriodicalId":12250,"journal":{"name":"Expert Opinion on Drug Metabolism & Toxicology","volume":"18 1","pages":"261 - 275"},"PeriodicalIF":4.3,"publicationDate":"2022-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45983648","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-04-03DOI: 10.1080/17425255.2022.2080052
Cornélie Fanton D'Andon, Patricia Correia, J. Rigaill, B. Kably, Sophie Périnel-Ragey, M. Launay
ABSTRACT Introduction Ceftazidime is used for the treatment of many bacterial infections, including severe P. aeruginosa infections. Like other beta-lactams, inter-individual variability in ceftazidime pharmacokinetics has been described. Due to its related pathophysiological modifications, obesity might influence ceftazidime pharmacokinetics. Areas covered The objective of this review is to assess the current state of knowledge about the impact of obesity on ceftazidime treatment. A literature search was conducted on PubMed-MEDLINE (2016–2021) to retrieve pharmacokinetic studies published in English, matching the terms ‘ceftazidime’ AND ‘pharmacokinetics.’ Expert opinion The impact of obesity on pharmacokinetics is generally poorly known, mainly because obese patients are often excluded from clinical studies. However, the published literature clearly shows that obese patients have significantly lower ceftazidime concentrations. This could be explained by increased volume of distribution and clearance. This low exposure represents a major factor of therapeutic failure, potentially fatal for critically ill patients. While further studies would be useful to better assess the magnitude and understanding of this variability, the use of higher doses of ceftazidime is needed in obese patients. Moreover, therapeutic drug monitoring for dose adaptation is of major interest for these patients, as the efficacy of ceftazidime seems to be directly related to its plasma concentration.
{"title":"Ceftazidime dosing in obese patients: is it time for more?","authors":"Cornélie Fanton D'Andon, Patricia Correia, J. Rigaill, B. Kably, Sophie Périnel-Ragey, M. Launay","doi":"10.1080/17425255.2022.2080052","DOIUrl":"https://doi.org/10.1080/17425255.2022.2080052","url":null,"abstract":"ABSTRACT Introduction Ceftazidime is used for the treatment of many bacterial infections, including severe P. aeruginosa infections. Like other beta-lactams, inter-individual variability in ceftazidime pharmacokinetics has been described. Due to its related pathophysiological modifications, obesity might influence ceftazidime pharmacokinetics. Areas covered The objective of this review is to assess the current state of knowledge about the impact of obesity on ceftazidime treatment. A literature search was conducted on PubMed-MEDLINE (2016–2021) to retrieve pharmacokinetic studies published in English, matching the terms ‘ceftazidime’ AND ‘pharmacokinetics.’ Expert opinion The impact of obesity on pharmacokinetics is generally poorly known, mainly because obese patients are often excluded from clinical studies. However, the published literature clearly shows that obese patients have significantly lower ceftazidime concentrations. This could be explained by increased volume of distribution and clearance. This low exposure represents a major factor of therapeutic failure, potentially fatal for critically ill patients. While further studies would be useful to better assess the magnitude and understanding of this variability, the use of higher doses of ceftazidime is needed in obese patients. Moreover, therapeutic drug monitoring for dose adaptation is of major interest for these patients, as the efficacy of ceftazidime seems to be directly related to its plasma concentration.","PeriodicalId":12250,"journal":{"name":"Expert Opinion on Drug Metabolism & Toxicology","volume":"18 1","pages":"277 - 284"},"PeriodicalIF":4.3,"publicationDate":"2022-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44883749","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-04-03DOI: 10.1080/17425255.2022.2086121
C. A. Buzea, L. Dima, C. Correll, P. Manu
ABSTRACT Introduction Antipsychotics represent the mainstay in the treatment of patients diagnosed with major psychiatric disorders. Hypertension, among other components of metabolic syndrome, is a common finding in these patients. For their psychiatric and physical morbidity, many patients receive polypharmacy, exposing them to the risk of clinically relevant drug–drug interactions. Areas covered This review summarizes the knowledge regarding the known or potential drug–drug interactions between antipsychotics and the main drug classes used in the treatment of hypertension. We aimed to provide the clinician an insight into the pharmacokinetic and pharmacodynamic interactions between these drugs for a better choice of combinations of drugs to treat both the mental illness and cardiovascular risk factors. For this, we performed a literature search in PubMed and Scopus databases, up to 31 July 2021. Expert opinion The main pharmacokinetic interactions between antipsychotics and antihypertensive drugs involve mainly the cytochrome P450 system. The pharmacodynamic interactions are produced by multiple mechanisms, leading to concurrent binding to the same receptors. The data available regarding drug–drug interactions is mostly based on case reports and small studies and therefore should be interpreted with caution. The current knowledge is sufficiently strong to guide clinicians in selecting safer drug combinations as summarized here.
{"title":"Drug–drug interactions involving antipsychotics and antihypertensives","authors":"C. A. Buzea, L. Dima, C. Correll, P. Manu","doi":"10.1080/17425255.2022.2086121","DOIUrl":"https://doi.org/10.1080/17425255.2022.2086121","url":null,"abstract":"ABSTRACT Introduction Antipsychotics represent the mainstay in the treatment of patients diagnosed with major psychiatric disorders. Hypertension, among other components of metabolic syndrome, is a common finding in these patients. For their psychiatric and physical morbidity, many patients receive polypharmacy, exposing them to the risk of clinically relevant drug–drug interactions. Areas covered This review summarizes the knowledge regarding the known or potential drug–drug interactions between antipsychotics and the main drug classes used in the treatment of hypertension. We aimed to provide the clinician an insight into the pharmacokinetic and pharmacodynamic interactions between these drugs for a better choice of combinations of drugs to treat both the mental illness and cardiovascular risk factors. For this, we performed a literature search in PubMed and Scopus databases, up to 31 July 2021. Expert opinion The main pharmacokinetic interactions between antipsychotics and antihypertensive drugs involve mainly the cytochrome P450 system. The pharmacodynamic interactions are produced by multiple mechanisms, leading to concurrent binding to the same receptors. The data available regarding drug–drug interactions is mostly based on case reports and small studies and therefore should be interpreted with caution. The current knowledge is sufficiently strong to guide clinicians in selecting safer drug combinations as summarized here.","PeriodicalId":12250,"journal":{"name":"Expert Opinion on Drug Metabolism & Toxicology","volume":" 44","pages":"285 - 298"},"PeriodicalIF":4.3,"publicationDate":"2022-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41253625","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-04-01Epub Date: 2022-06-08DOI: 10.1080/17425255.2022.2081148
Emily N Drwiega, Nicole C Griffith, Larry H Danziger
Introduction: Cefiderocol is a siderophore cephalosporin antibiotic and first of its kind approved by the Food and Drug Administration for the treatment of complicated urinary tract infections (cUTI) and hospital-acquired and ventilator-associated bacterial pneumonia (HABP/VABP) in patients 18 years or older caused by susceptible organisms. Cefiderocol's unique mechanism of iron chelation improves Gram-negative membrane penetration as the bacteria's iron uptake mechanism recognizes the chelated iron antibiotic and iron for entry. This also allows for the evasion of cefiderocol from cell entry-related resistance mechanisms.
Areas covered: This review covers the mechanism of action, resistance mechanisms, pharmacokinetics in various patient populations, and pharmacodynamics. Relevant literature evaluating efficacy and safety are discussed.
Expert opinion: Limited treatment options are available for the treatment of carbapenem-resistantorganisms. Clinical trials have demonstrated that cefiderocol is no worse than alternative treatment options for cUTIs and HABP/VABP, but more data are currently available to support the use of beta-lactam beta-lactamase inhibitor agents, where susceptible. Mortality differences demonstrated in patients with pneumonia and bloodstream infections must further be explored and logistical and practical considerations regarding susceptibility testing and use as monotherapy vs. combination therapy must be considered prior to confidently recommending cefiderocol for regular use in systemic infections.
{"title":"Pharmacokinetic evaluation of cefiderocol for the treatment of multidrug resistant Gram-negative infections.","authors":"Emily N Drwiega, Nicole C Griffith, Larry H Danziger","doi":"10.1080/17425255.2022.2081148","DOIUrl":"10.1080/17425255.2022.2081148","url":null,"abstract":"<p><strong>Introduction: </strong>Cefiderocol is a siderophore cephalosporin antibiotic and first of its kind approved by the Food and Drug Administration for the treatment of complicated urinary tract infections (cUTI) and hospital-acquired and ventilator-associated bacterial pneumonia (HABP/VABP) in patients 18 years or older caused by susceptible organisms. Cefiderocol's unique mechanism of iron chelation improves Gram-negative membrane penetration as the bacteria's iron uptake mechanism recognizes the chelated iron antibiotic and iron for entry. This also allows for the evasion of cefiderocol from cell entry-related resistance mechanisms.</p><p><strong>Areas covered: </strong>This review covers the mechanism of action, resistance mechanisms, pharmacokinetics in various patient populations, and pharmacodynamics. Relevant literature evaluating efficacy and safety are discussed.</p><p><strong>Expert opinion: </strong>Limited treatment options are available for the treatment of carbapenem-resistantorganisms. Clinical trials have demonstrated that cefiderocol is no worse than alternative treatment options for cUTIs and HABP/VABP, but more data are currently available to support the use of beta-lactam beta-lactamase inhibitor agents, where susceptible. Mortality differences demonstrated in patients with pneumonia and bloodstream infections must further be explored and logistical and practical considerations regarding susceptibility testing and use as monotherapy vs. combination therapy must be considered prior to confidently recommending cefiderocol for regular use in systemic infections.</p>","PeriodicalId":12250,"journal":{"name":"Expert Opinion on Drug Metabolism & Toxicology","volume":"18 1","pages":"245-259"},"PeriodicalIF":4.3,"publicationDate":"2022-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43385940","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}