Dasatinib-induced spleen contraction leads to transient lymphocytosis

Pubmed-Investigación

Blood Adv. 2022 Dec 30:bloodadvances.2022009279. doi: 10.1182/bloodadvances.2022009279. Online ahead of print. ABSTRACT The tyrosine kinase inhibitor dasatinib is approved for Philadelphia chromosome positive leukemia, including chronic myeloid leukemia (CML). While effective and well tolerated, patients typically exhibit a transient lymphocytosis following dasatinib uptake. The underlying physiological process linking dasatinib to lymphocytosis has remained unknown to…

The second-generation antipsychotic drug aripiprazole modulates the serotonergic system in pancreatic islets and induces beta cell dysfunction in female mice

Pubmed-Investigación

Diabetologia. 2022 Mar;65(3):490-505. doi: 10.1007/s00125-021-05630-0. Epub 2021 Dec 21. ABSTRACT AIMS/HYPOTHESIS: Second-generation antipsychotic (SGA) drugs have been associated with the development of type 2 diabetes and the metabolic syndrome in patients with schizophrenia. In this study, we aimed to investigate the effects of two different SGA drugs, olanzapine and aripiprazole, on metabolic state and islet…

Modulation of hypothalamic AMPK phosphorylation by olanzapine controls energy balance and body weight

Pubmed-Investigación

Metabolism. 2022 Dec;137:155335. doi: 10.1016/j.metabol.2022.155335. Epub 2022 Oct 19. ABSTRACT BACKGROUND: Second-generation antipsychotics (SGAs) are a mainstay therapy for schizophrenia. SGA-treated patients present higher risk for weight gain, dyslipidemia and hyperglycemia. Herein, we evaluated the effects of olanzapine (OLA), widely prescribed SGA, in mice focusing on changes in body weight and energy balance. We further…

CYP2C8*3 and *4 define CYP2C8 phenotype: An approach with the substrate cinitapride

Pubmed-Investigación

Clin Transl Sci. 2022 Nov;15(11):2613-2624. doi: 10.1111/cts.13386. Epub 2022 Sep 6. ABSTRACT Cinitapride is a gastrointestinal prokinetic drug, prescribed for the treatment of functional dyspepsia, and as an adjuvant therapy for gastroesophageal reflux disease. In this study, we aimed to explore the impact of relevant variants in CYP3A4 and CYP2C8 and other pharmacogenes, along with…

Association between CYP2C19 and CYP2B6 phenotypes and the pharmacokinetics and safety of diazepam

Pubmed-Investigación

Biomed Pharmacother. 2022 Nov;155:113747. doi: 10.1016/j.biopha.2022.113747. Epub 2022 Sep 24. ABSTRACT Diazepam is a benzodiazepine (BZD) used worldwide for a variety of conditions. Long-term use of diazepam increases the risk for developing tolerance and dependence and for the occurrence of adverse drug reactions (ADRs). CYP3A4 and CYP2C19 mainly metabolize diazepam and are therefore the primary…

Bioavailability of Oniria®, a Melatonin Prolonged-Release Formulation, Versus Immediate-Release Melatonin in Healthy Volunteers

Pubmed-Investigación

Drugs R D. 2022 Sep;22(3):235-243. doi: 10.1007/s40268-022-00394-3. Epub 2022 Aug 2. ABSTRACT BACKGROUND: Melatonin is an endogenous substance which plays a key role in sleep induction by reducing sleep onset latency; it has been approved by the European Food Safety Authority as a food supplement for exogenous administration. Oniria® is a food supplement formulated as…

Polymorphism of Drug Transporters, Rather Than Metabolizing Enzymes, Conditions the Pharmacokinetics of Rasagiline

Pubmed-Investigación

Pharmaceutics. 2022 Sep 21;14(10):2001. doi: 10.3390/pharmaceutics14102001. ABSTRACT Rasagiline is a selective and irreversible inhibitor of monoamine oxidase type B with neuroprotective effect, indicated for the management of Parkinson’s disease. The aim of this work was to evaluate the impact of seven CYP1A2 alleles and of 120 additional variants located in other CYP enzymes (e.g., CYP2C19),…