Drug Metabolism Letters

BACKGROUND: Neurological complications are most likely to be fatal and cause loss of ability to function or care for self. These include Alzheimer's disease and cognitive impairment. The main aim of the review is to determine the effects of various drugs and their cognitive risk with the need to opt for herbal therapy as an adjuvant in treating neurological conditions like Alzheimer's disease with lesser-known side effects. The Methodology: Involved a detailed literature survey which was performed through an online database, such as Science Direct, Google Scholar, Scopus, Cochrane, and PubMed...

The use of pharmacotherapy for improving healthcare in society is increasing. A vast majority of patients have either received subtherapeutic treatment (which could result from low pharmacokinetic) or experienced adverse effects due to the toxic levels of the drug. The medicines used to treat chronic conditions, such as epilepsy; cardiovascular diseases; and oncological, neurological, and psychiatric disorders, require routine monitoring. New targeted therapies suggest an individualized treatment that can slowly move practitioners away from the concept of a one-size-fits-all-fixed-dosing approach...

BACKGROUND: Herbal products have been derived from different natural sources, mainly used as a source of food material and medicine in the health sectors since very ancient time. Herbal products have gained popularity in the modern medicine due to its health beneficial properties and pharmacological activities. Flavonoids are an important class of secondary metabolites found to be present in the medicinal plants and their derived products. Flavonoids has been known for their anti-allergic, anti-bacterial, anti-diabetic, anti-inflammatory, anti-viral, anti-proliferative, anti-mutagenic, anti-thrombotic, anti-carcinogenic, anti-oxidant and hepatoprotective activities in the medicine...

Coronaviruses cause disease in human and animals. In 2019 a novel coronavirus was first characterized in Wuhan, China. It causes acute respiratory disease and designated the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or COVID-19. The COVID-19 spread to all cities of China, and in 2020 to the whole world. Patients with COVID-19 may recover without medical treatment. However, some patients need medical care. The Cytochrome p450s (CYP450s) are large superfamily of enzymes catalyze the metabolism of endogenous substrates and xenobiotics...

BACKGROUND: Identification of clinical drug-drug interaction (DDI) risk is an important aspect of drug discovery and development owing to poly-pharmacy in present-day clinical therapy. Drug metabolizing enzymes (DME) plays important role in the efficacy and safety of drug candidates. Hence evaluation of a New Chemical Entity (NCE) as a victim or perpetrator is very crucial for DDI risk mitigation. ZY12201 (2-((2-(4-(1H-imidazol-1-yl) phenoxy) ethyl) thio)-5-(2-(3, 4- dimethoxy phenyl) propane-2-yl)-1-(4-fluorophenyl)-1H-imidazole) is a novel and potent Takeda-G-protein-receptor-5 (TGR-5) agonist...

OBJECTIVE: To explore the human in vivo metabolism of SEP-227900 (4H-furo[3, 2-b]pyrrole-carboxylic acid, m.w 151.03), a D-amino-acid oxidase (DAAO) inhibitor by using plasma and urine samples from first-in-human study. METHODS: The human plasma and urine samples were from a single dose cohort that consisted of 9 healthy male volunteers each received 80-mg dose of SEP-227900 orally. The pooled pre-dose urine and the pooled 0-24 h urine sample were created across 9 subjects by equal volume...

BACKGROUND: In this study, we focused primarily on three anti-malarial drugs that were tested against two malarial targets. Anti-malarial drugs like chloroquine, mefloquine, proguanil were chosen, while DHFR and GST targets from human malaria parasites such as Plasmodium falciparum, Plasmodium malariae, Plasmodium ovale, Plasmodium vivax were considered for the study. OBJECTIVE: The purpose of this study was to determine the sequence and structural similarity of proteins DHFR and GST among four Plasmodium species as well as to discover in silico interactions with aforementioned drug candidates...

BACKGROUND & OBJECTIVE: Compound X is a drug candidate for the treatment of neurodegenerative diseases. Its brain distribution was evaluated as part of the lead identification and optimization of early drug discovery. METHODS: The brain distribution of compound X was studied in genetic transporter knockout rodent models, in vivo models with a chemical inhibitor and in vitro transporter cell systems. RESULTS: Compound X was found to be a substrate for human Breast Cancer-Resistance Protein (BCRP) in vitro (efflux ratio 8...

BACKGROUND: Enflicoxib is a non-steroidal anti-inflammatory drug of the coxib family characterized by a long-lasting pharmacological activity that has been attributed to its active metabolite E-6132. OBJECTIVE: The aim of this work was to explore enflicoxib biotransformation in vitro in humans, rats and dogs, and to determine its metabolic pathways. METHOD: Different in vitro test systems were used, including hepatocytes and liver and non-hepatic microsomes...

BACKGROUNDS: Plants and their derived products have been used in the traditional system of medicine for the treatment of various forms of human disorders since very ancient time. In the traditional system of medicine and modern allopathic medicine, numerous phytoconstituents have been used for the preparation of various types of formulation. Flavonoidal class phytochemicals are the main active phytoconstituents of plants, fruit, vegetables and beverages. Flavonoidal class phytochemicals are more referred as "nutraceuticals" due to their important pharmacological activities in the mammalian body...

BACKGROUND: Kidney disease associated with cancer and anti-cancer therapies has been increasingly recognized in the field of Onco-nephrology. In particular, drug-induced nephrotoxicity has necessary implications since most chemotherapeutic agents have nephrotoxic potential. Also, standard creatinine clearance methods used to measure kidney function have been questioned in cancer patients due to factors like low muscle mass and poor nutritional status. Overestimations of the glomerular filtration rate not only increase the nephrotoxic potential of different agents but also can further limit the use of first-line therapies...

BACKGROUND: The pharmacodynamic effects of digoxin are susceptible to multiple factors, most notably, heart uptake of the digoxin dose and its concentration in the serum. Another important factor to mention is the renal function state of an individual. OBJECTIVE: In this study, we aimed to develop a simple algorithm based on subsets of clinically relevant information, which will help to personalize digoxin based on pharmacokinetic (PK) approach, which can help on marketing the appropriate utilization of this medication...

A typographical error appeared in the author's name of the article entitled "Inhibitory Effect of Codeine on Sucrase Activity" by Dariush Minai-Tehrani, Saeed Minoui, Marzie Sepehre, Zohre Sharif-Khodai, Tooka Aavani, Drug Metabolism Letters, 2009; 3(1): 58-60. [1]. Details of the error and a correction are provided here. The fourth author's name in this article was misspelled. Hence it should be read as "Zohreh Sharifkhodaei" as per the request of the author. We regret the error and apologize to readers. The original article can be found online at: https://www...

BACKGROUND: Glutathione S-transferases (GSTs) are phase II metabolic enzymes crucial for the metabolism of electrophilic drugs. Additionally, several GST isoforms are involved in protein- protein interaction with mitogen-activated protein kinases (MAPKs), modulating apoptosis pathways. METHODS: To assess the potential change of enzymatic activity, we performed a GST enzyme assay with human recombinant GSTM1 in the presence and absence of MAPK8. Recently, GSTM1 has been demonstrated to interact with MAPK8 both in silico and in vitro...

Cysteine is one of the major intermediate products of cellular amino-acid metabolism. It is a semi-essential amino acid for protein synthesis. Besides, it is also employed in the regulation of major endogenous anti-oxidant molecule i.e., reduced glutathione (GSH). Further, it is a precursor of multiple sulfur-containing molecules like hydrogen sulfide, lanthionine, taurine, coenzyme A and biotin. It is also one of the key molecules for post-translational modifications of various cellular proteins. In physiological conditions, it is employed in the sulfhydration process and plays a key role in the physiology modification of the inflammatory process in various organs, including the neurological system...

AIMS: The study was aimed at exploring the role of Acetyl L-Carnitine supplementation attenuating dementia and degradation of cognitive abilities in Hyperhomocysteinemia induced AD manifestations in the mouse model. BACKGROUND: Alzheimer's disease (AD) is a neurological disorder that is marked by dementia, and degradation of cognitive abilities. There is great popularity gained by natural supplements as the treatment for AD, due to the higher toxicities of synthetic drugs...

The liver plays a crucial role in endogenous metabolic activity and homeostasis of macro and micronutrients. Further, it acts as a metabolic hub in mammals, where the ingested food-derived nutrients and xenobiotics or drugs are metabolized for utilization and/or excretion through its enzymatic and non-enzymatic machinery. Nutritional deficiency, one of the major public health problems, is associated with global disease burden, including pulmonary tuberculosis (PTB) caused by Mycobacterium tuberculosis (Mtb) infection...

BACKGROUND: Methods to provide absolute quantitation of the administered drug and corresponding metabolites in tissue in a spatially resolved manner is a challenging but much needed capability in pharmaceutical research. Quantitative Whole-Body Autoradiography (QWBA) after a single- dose intravenous (3 mg/kg) and extravascular (30 mg/kg) administrations of an in vitro metabolically stable test compound (structure not reported here) indicated quick tissue distribution and excretion. OBJECTIVE: Good bioavailability and short in vivo half-lives were determined formerly for the same test compound...

BACKGROUND: A group of substituted benzothiazoles from a research project was found to have low microsomal clearance. However, these compounds had very high clearance in vivo. METHODS: In the present study, the clearance mechanism of two of the structural analogs, was investigated in vitro and in vivo. RESULTS: In vitro studies showed the formation of corresponding non-P450 dependent oxidative metabolites in S9, cytosol, and hepatocytes. The in vitro formation of these metabolites was observed in mice, rats, non-human primates, and humans...

Due to its easy availability, rapid and severe toxicity, and no specific antidote, aluminum phosphide has emerged as a lethal toxin, commonly used for suicidal intent in agricultural communities. Despite various advances in medicine, this compound's toxicity is poorly understood, and it still has a very high case fatality rate with no definitive treatment options available. This review aims to understand the mechanism of toxicity, clinical toxidrome of acute aluminum phosphide poisoning, and the available therapeutic options, including recent advances...