Current Drug Metabolism - Volume 25, Issue 2, 2024

Background: Fluoropyrimidine-induced toxicity is a main limitation of therapy. Currently, polymorphisms in the DPYD gene, which encodes the 5-FU activation enzyme dihydropyrimidine dehydrogenase (DPD), are used to adjust the dosage and prevent toxicity. Despite the predictive value of DPYD genotyping, a great proportion of fluoropyrimidine toxicity cannot be solely explained by DPYD variations. Objective: We herein su Read More

Asunaprevir, daclatasvir, and beclabuvir are direct-acting antiviral agents used in the treatment of patients infected with hepatitis C genotype 1b. This article reviews the biotransformation and disposition of these drugs in relation to the safety and efficacy of therapy. CYP3A4 and 3A5 catalyze the oxidative biotransformation of the drugs, while P-glycoprotein mediates their efflux from tissues. Asunaprevir is also a substrate for t Read More

Preserving host health and homeostasis is largely dependent on the human gut microbiome, a varied and ever-changing population of bacteria living in the gastrointestinal tract. This article aims to explore the multifaceted functions of the gut microbiome and shed light on the evolving field of research investigating the impact of herbal medicines on both the composition and functionality of the gut microbiome. Through a co Read More

Aims: Pharmacogenomics has been identified to play a crucial role in determining drug response. The present study aimed to identify significant genetic predictor variables influencing the therapeutic effect of paracetamol for new indications in preterm neonates. Background: Paracetamol has recently been preferred as a first-line drug for managing Patent Ductus Arteriosus (PDA) in preterm neonates. Single Nucleotide Pol Read More

Background: Prusogliptin is a potent and selective DPP-4 inhibitor. In different animal models, Prusogliptin showed potential efficacy in the treatment of type 2 diabetes. However, the knowledge of its pharmacokinetics and safety in patients with liver dysfunction is limited. Objectives: The present study evaluated the pharmacokinetics and safety of Prusogliptin in subjects with mild or moderate hepatic impairment com Read More

Aims: To evaluate the association between rs4680 polymorphism in the COMT gene and the vasoconstrictive effects of commonly used vasopressors. Background: Dopamine is a medication that is given intravenously to critically ill patients to help increase blood pressure. Catechol O-Methyl Transferase (COMT) breaks down dopamine and other catecholamines. There is a genetic variation in the COMT gene called rs46 Read More

Aim: The aim of this study was to investigate the metabolism of Gelsemium elegans in human, pig, goat and rat liver microsomes and to elucidate the metabolic pathways and cleavage patterns of the Gelsemium alkaloids among different species. Methods: A human, goat, pig and rat liver microsomes were incubated in vitro. After incubating at 37°C for 1 hour and centrifuging, the processed samples were detected by HPL Read More

Background: Remimazolam (RMZ) is a novel ultrashort-acting benzodiazepine used for sedation by intravenous administration. The pharmacophore of RMZ includes a carboxyl ester group sensitive to esterase- mediated hydrolysis, which is the primary path of metabolic elimination. However, for the sake of drug safety, a deeper and broader knowledge of the involved metabolic pathways and the evolving metabolites is required. I Read More

Objective: This study aimed to investigate the effects of clarithromycin and ketoconazole on the pharmacokinetic properties of tacrolimus in different CYP3A4 genotype recombinant metabolic enzyme systems, so as to understand the drug interactions and their mechanisms further. Method: The experiment was divided into three groups: a blank control group, CYP3A4*1 group and CYP3A4*18 recombinant enzyme gr Read More