Exome Sequence Data of Eight SLC Transporters Reveal That and Variants Alter Metformin Pharmacokinetics and Glycemic Control.

: Type 2 diabetes (T2D) is one of the leading causes of mortality and is a public health challenge worldwide. Metformin is the first-choice treatment for T2D; its pharmacokinetics (PK) is facilitated by members of the solute carrier (SLC) superfamily of transporters, it is not metabolized, and it is excreted by the kidney. Although interindividual variability in metformin pharmacokinetics is documented in the Mexican population, its pharmacogenomics is still underexplored.

Phytochemicals That Interfere With Drug Metabolism and Transport, Modifying Plasma Concentration in Humans and Animals.

Phytochemicals (Pch) present in fruits, vegetables and other foods, are known to inhibit or induce drug metabolism and transport. An exhaustive search was performed in five databases covering from 2000 to 2021. Twenty-one compounds from plants were found to modulate CYP3A and/or P-gp activities and modified the pharmacokinetics and the therapeutic effect of 27 different drugs.

Comparative Bioavailability and Pharmacokinetics Between the Solid Form of Metformin vs a Novel Liquid Extemporaneous Formulation in Children.

Metformin pharmacokinetics in a liquid extemporaneous formulation from commercial tablets was determined in paediatric patients. A randomized, transversal clinical trial was conducted in 34 children and adolescents between 7 and 17 years of age. 17 children were randomized to take metformin in the liquid formulation and, after a 1-week wash period, a 500 mg metformin tablet was administered to them.

The L125F MATE1 variant enriched in populations of Amerindian origin is associated with increased plasma levels of metformin and lactate.

Genetic factors that affect variability in metformin response have been poorly studied in the Latin American population, despite its being the initial drug therapy for type 2 diabetes, one of the most prevalent diseases in that region. Metformin pharmacokinetics is carried out by members of the membrane transporters superfamily (SLCs), being the multidrug and toxin extrusion protein 1 (MATE1), one of the most studied. Some genetic variants in MATE1 have been associated with reduced in vitro metformin transport.

Baclofen in the Therapeutic of Sequele of Traumatic Brain Injury: Spasticity.

Traumatic brain injury (TBI) is an alteration in brain function, caused by an external force, which may be a hit on the skull, rapid acceleration or deceleration, penetration of an object, or shock waves from an explosion. Traumatic brain injury is a major cause of morbidity and mortality worldwide, with a high prevalence rate in pediatric patients, in which treatment options are still limited, not available at present neuroprotective drugs. Although the therapeutic management of these patients is varied and dependent on the severity of the injury, general techniques of drug types are handled, as well as physical and surgical.

A New Method to Quantify Ifosfamide Blood Levels Using Dried Blood Spots and UPLC-MS/MS in Paediatric Patients with Embryonic Solid Tumours.

Ifosfamide blood concentrations are necessary to monitor its therapeutic response, avoiding any adverse effect. We developed and validated an analytical method by UPLC-MS/MS to quantify ifosfamide in dried blood spots (DBS). Blood samples were collected on Whatman 903® filter paper cards.

Extemporaneous Formulations of Metformin for Pediatric Endocrinology: Physicochemical Integrity, Cytotoxicity of Sweeteners, and Quantitation of Plasma Levels.

Purpose: In response to the lack of pediatric formulations of metformin to control type 2 diabetes mellitus, hyperinsulinemic obesity, and dyslipidemias, we developed liquid formulations of metformin by dissolving 3 generic brands of 500-mg metformin(*,)(†,)(‡) tablets in water sweetened with sucralose. The physicochemical stabilities of these drugs were assessed and compared with those of formulations made with the innovative brand of metformin.(∥) A method to measure metformin plasma levels was proposed and then tested in 2 healthy subjects.

Comparison between the antiproliferative effect and intracellular glutathione depletion induced by Casiopeína IIgly and cisplatin in murine melanoma B16 cells.

Background: Casiopeína IIgly (Cas IIgly) [Cu(4,7-dimethyl-1,10-phenanthroline)(glycinate)]NO(3) induce oxidative damage in different human tumour cell strains, as the known anticancer agent cisplatin (CDDP) does.

Purpose: To compare glutathione (GSH) depletion induced by Cas IIgly and CDDP in murine melanoma B16 cells and its relationship with their antiproliferative effect.

Materials And Methods: Cell growth was determined according to the sulforhodamine B assay.

A reliable method of liquid chromatography for the quantification of acetaminophen and identification of its toxic metabolite N-acetyl-p-benzoquinoneimine for application in pediatric studies.

The aim of the present study was to develop a simple, selective and reliable method to quantify acetaminophen and its toxic metabolite N-acetyl-p-benzoquinoneimine (NAPQI) for pediatric studies using 100 µL plasma samples, by reverse-phase HPLC and UV detection. The assay was performed using a C₁₈ column and an isocratic elution with water-methanol-formic acid (70:30:0.15; v/v/v) as mobile phase.

Casiopeína IIgly induced cytotoxicity to HeLa cells depletes the levels of reduced glutathione and is prevented by dimethyl sulfoxide.

The newly synthesized copper coordination compound Casiopeína IIgly (Cas IIgly) is a promising alternative drug in the treatment of cancer, since it has shown cytotoxicity and genotoxicity in different tumour models. Given its enhanced effects after ascorbic acid-mediated copper reduction, Cas IIgly's activity is thought to be related to oxidative damage. In the present work, oxidized Cas IIgly failed to induce cytosolic oxidative damage in HeLa cells (only 0.

Induction of oxidative damage by copper-based antineoplastic drugs (Casiopeínas).

Purpose: The aim of the present study is to determine in HeLa cells and in human lymphocytes, by an easy and fast method, the induction of oxidative damage to plasma membrane lipids and nuclear DNA by Casiopeínas, which are recently synthesized coordination complexes that have been considered as a promising chemotherapeutic alternative for the treatment of cancer, since they have shown cytotoxicity and genotoxicity in several cancer cell lines and xenotransplanted tumours. The presence of an oxidized copper atom in their structure strongly suggests that their mode of action seems to be related to reactive oxygen species (ROS) generation after copper atom reduction through the Fenton and Haber-Weiss system.

Method: Lipid peroxidation was evaluated as thiobarbituric acid reactive malondialdehyde, cytotoxicity by the fluorescein diacetate/ethidium bromide stain and genotoxicity as DNA fragmentation by the comet assay.