02bde3c820badfe18943f447f4f0656f 309004.pdf 803d4405a4929dafb36e42285fb496009135d93d 309004.pdf b0e27f60f5292d7555e95832c849df72f3b6d61fdc7e0b696c82de457f7cbc4a 309004.pdf Title: Metabolic Syndrome Drug Therapy: The Potential Interplay of Pharmacogenetics and Pharmacokinetic Interactions in Clinical Practice: A Narrative Review Subject: Metabolic syndrome (MetS) presents a significant global health challenge, characterized by a cluster of metabolic alterations including obesity, hypertension, insulin resistance/dysglycemia, and atherogenic dyslipidemia. Advances in understanding and pharmacotherapy have added complexity to MetS management, particularly concerning drug interactions and pharmacogenetic variations. Limited literature exists on drug–drug–gene interactions (DDGIs) and drug–drug–transporter gene interactions (DDTGIs), which can significantly impact pharmacokinetics and pharmacodynamics, affecting treatment outcomes. This narrative review aims to address the following three key objectives: firstly, shedding a light on the PK metabolism, transport, and the pharmacogenetics (PGx) of medicines most commonly used in the MetS setting (relevant lipid-lowering drugs, antihypertensives and antihyperglycemics agents); secondly, exemplifying potential clinically relevant pharmacokinetic drug interactions, including drug–drug interactions, DDGIs, and DDTGIs; and, thirdly, describing and discussing their potential roles in clinical practice. This narrative review includes relevant information found with the use of interaction checkers, pharmacogenetic databases, clinical pharmacogenetic practice guidelines, and literature sources, guided by evidence-based medicine principles. Keywords: metabolic syndrome; pharmacogenetics; pharmacokinetics; drug–drug–transporter gene interactions; drug–drug-gene interactions; lipid-lowering agents; antihypertensives; antihyperglycemics; clinical decision making Author: Sandra Knežević, Francesca Filippi-Arriaga, Andrej Belančić, Tamara Božina, Jasenka Mršić-Pelčić and Dinko Vitezić Creator: LaTeX with hyperref Producer: pdfTeX-1.40.25 CreationDate: Tue Sep 3 12:16:26 2024 CEST ModDate: Tue Sep 3 12:20:12 2024 CEST Custom Metadata: no Metadata Stream: no Tagged: no UserProperties: no Suspects: no Form: none JavaScript: no Pages: 24 Encrypted: no Page size: 595.276 x 841.89 pts (A4) Page rot: 0 File size: 406938 bytes Optimized: no PDF version: 1.7 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- OPZDHV+VnURWPalladioL Type 1 Custom yes yes yes 10 0 QQSSOQ+URWPalladioL-Bold Type 1 Custom yes yes yes 16 0 LXQCFR+URWPalladioL-Roma Type 1 Custom yes yes yes 22 0 ZXJBIW+URWPalladioL-Ital Type 1 Custom yes yes yes 27 0 QHMKWQ+PazoMath Type 1 Builtin yes yes yes 66 0 LWLIVD+EURM10 Type 1 Builtin yes yes yes 92 0 MXDKUP+CMSY10 Type 1 Builtin yes yes yes 107 0 Jhove (Rel. 1.28.0, 2023-05-18) Date: 2025-03-15 02:43:00 CET RepresentationInformation: 309004.pdf ReportingModule: PDF-hul, Rel. 1.12.4 (2023-03-16) LastModified: 2025-03-14 13:29:15 CET Size: 406938 Format: PDF Version: 1.7 Status: Well-Formed and valid SignatureMatches: PDF-hul MIMEtype: application/pdf PDFMetadata: Objects: 648 FreeObjects: 1 IncrementalUpdates: 0 DocumentCatalog: PageLayout: SinglePage PageMode: UseNone Outlines: Item: Title: Introduction Destination: section.1 Item: Title: Methodology Destination: section.2 Item: Title: Pharmacogenetics of Lipid-Lowering Drug Drugs Destination: section.3 Children: Item: Title: 3-Hydroxy-3-Methylglutaryl-Coenzyme A Reductase (HMG-CoA Reductase) Inhibitors Destination: subsection.3.1 Item: Title: Fibrates Destination: subsection.3.2 Item: Title: Selective Cholesterol Absorption Inhibitors Destination: subsection.3.3 Item: Title: Novel Lipid-Lowering Drugs Destination: subsection.3.4 Children: Item: Title: Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) Inhibitors Destination: subsubsection.3.4.1 Item: Title: Inclisiran Destination: subsubsection.3.4.2 Item: Title: Pharmacogenetics of Antihypertensive Drugs Destination: section.4 Children: Item: Title: Beta-Blockers (BB) Destination: subsection.4.1 Item: Title: Calcium Channel Blockers (CCBs) Destination: subsection.4.2 Item: Title: Angiotensin Receptor Blockers (ARBs) Destination: subsection.4.3 Item: Title: Angiotensin Converting Enzyme Inhibitors (ACEIs) Destination: subsection.4.4 Item: Title: Vasodilators Destination: subsection.4.5 Item: Title: Pharmacogenetics of Antihyperglycemic Drugs Destination: section.5 Children: Item: Title: Biguanides Destination: subsection.5.1 Item: Title: Thiazolidinedinones (TZDs) Destination: subsection.5.2 Item: Title: Sulphonylureas (SU) Destination: subsection.5.3 Item: Title: Sodium Glucose Co-Transporter-2 Inhibitors (SGLT2i) Destination: subsection.5.4 Item: Title: Glucagon-like Peptide-1 Receptor Agonists (GLP1-RA) Destination: subsection.5.5 Item: Title: Dipeptidyl Peptidase-4 (DPP-4) Inhibitors Destination: subsection.5.6 Item: Title: Discussion Destination: section.6 Item: Title: References Destination: section.7 Info: Title: Metabolic Syndrome Drug Therapy: The Potential Interplay of Pharmacogenetics and Pharmacokinetic Interactions in Clinical Practice: A Narrative Review Author: こちのつひち〠かのづㅾづぶどㄇ〬〠うひちのっづびっち〠うどぬどばばど〭ぁひひどちでち〬〠ぁのつひづな〠あづぬちのㄍどㄇ〬〠ごちねちひち〠あはㅾどのち〬〠おちびづのにち〠きひㅡどㄇ〭ぐづぬㄍどㄇ〠ちのつ〠いどのには〠ざどぴづぺどㄇ Subject: Metabolic syndrome (MetS) presents a significant global health challenge, characterized by a cluster of metabolic alterations including obesity, hypertension, insulin resistance/dysglycemia, and atherogenic dyslipidemia. Advances in understanding and pharmacotherapy have added complexity to MetS management, particularly concerning drug interactions and pharmacogenetic variations. Limited literature exists on drug drug gene interactions (DDGIs) and drug drug transporter gene interactions (DDTGIs), which can significantly impact pharmacokinetics and pharmacodynamics, affecting treatment outcomes. This narrative review aims to address the following three key objectives: firstly, shedding a light on the PK metabolism, transport, and the pharmacogenetics (PGx) of medicines most commonly used in the MetS setting (relevant lipid-lowering drugs, antihypertensives and antihyperglycemics agents); secondly, exemplifying potential clinically relevant pharmacokinetic drug interactions, including drug drug interactions, DDGIs, and DDTGIs; and, thirdly, describing and discussing their potential roles in clinical practice. This narrative review includes relevant information found with the use of interaction checkers, pharmacogenetic databases, clinical pharmacogenetic practice guidelines, and literature sources, guided by evidence-based medicine principles. 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