Clinical pharmacokinetics and pharmacogenetics of tamoxifen and endoxifen

Introduction: Tamoxifen dominates the anti-estrogenic therapy in the early and metastatic breast cancer setting. Tamoxifen has a complex metabolism, being mainly metabolized by CYP2D6 into its 30–100 times more potent metabolite, endoxifen. Recently, a phase I study in which endoxifen as an orally z-endoxifen hydrochloride has been successfully evaluated.

Areas covered: the principal pharmacogenetic and non-genetic differences in the pharmacology of tamoxifen and endoxifen are evaluated. To this end, references from PubMed, Embase or Web of Science, among others, were reviewed As non-genetic factors, important differences and similarities such age, or adherence to tamoxifen therapy are comprehensively illustrated. Additionally, since CYP2D6 genotypes are considered the main limitation of tamoxifen, many studies have investigated the association between the worsened clinical outcomes in patients with non-functional CYP2D6 genotypes. In this review, an overview of the research on this field is presented. Also, a summary describing the literature about individualizing tamoxifen therapy with endoxifen concentrations and its limitations is listed.

Expert opinion: z-endoxifen hydrochloride is only investigated in the metastatic setting, still more research is required before its place in therapeutics is known. Similarly, monitoring tamoxifen efficacy based on endoxifen concentrations might not be overall recommended due to the limited evidence available.     

An Improved Method for the Synthesis of the of Indole[2,3-a]Pyrrolo[3,4-c]Carbazole-5,6-Dione N-Glycosides and their Cytotoxic Activity

Pharmaceutical Chemistry Journal - Use of formylindolylacetic acid as a reagent at the stage of preparing the glycosides of bis(indolyl)furan-2,5-diones and dioxane as solvent increased yields from...     

Multidisciplinary management of patients presenting with Lyme disease suspicion

Objective

The teaching hospital of Nancy, France, implemented a specific multidisciplinary care pathway (French acronym AMDPL) to improve the management of patients presenting with Lyme borreliosis (LB) suspicion. We aimed to assess the first year of activity of this care pathway.

Endothelial function,regulation of angiogenesis and embryonic central hemodynamics in ART-conceived pregnancies

Abstract

This study was undertaken to compare the concentrations of pro- and anti-angiogenic growth factors, nitric oxide (NO) stable metabolites in maternal serum and embryonic left ventricular (LV) isovolumic relaxation time (IRT, ms) during the first trimester in two groups of women: with pregnancy conceived by assisted reproductive technologies (ART, n?=?39) and normally conceived (control group, n?=?68) pregnancy. The concentration of vasoconstrictor endothelin 1 was 45.5 times more in ART than in control group. On the contrary, the concentrations of NO stable metabolites in ART were 1.9 times less than in control women. The assessment of angiogenic suppressors in ART women demonstrates the decrease in s-endoglin concentration was 1.6 times and in soluble receptor to vascular endothelial growth factor concentration was 2.0 times in comparison with control group. There was a significant increase in LV IRT in ART embryos in comparison to control ones. These data suggest significant changes in pro- anti-angiogenic factors balance and increase in vascular impedance in ART-conceived embryos.     

Inhibition of carbohydrate hydrolyzing enzymes associated with type 2 diabetes and antioxidative properties of some edible seeds in vitro

This study sought to evaluate the antioxidant properties and effects of some edible wild seeds [Afzelia africana Sm. (AFZ), Cyperus esculentus L. (CYP), Eleusine coracana Gaertn. (ELE), Irvingia gabonensis (Aubry-Lecomte ex O’Rorke) Baill. (IRV), Monodora myristica Dunal. (MON) and Parinari curatellifolia Planch. ex Benth. (PAR)] on α-amylase and α-glucosidase activities. The phenolic content and antioxidant activities of aqueous extracts of the seeds as typified by 1,1-diphenyl-2 picrylhydrazyl (DPPH) and hydroxyl (OH) radicals scavenging abilities and inhibition of Fe²⁺-induced malondialdehyde (MDA) production in rat’s pancreas in vitro were also assessed. ELE had significantly (p < 0.05) higher total phenol content than the other seeds; however, AFZ had the highest flavonoid content. The extracts scavenged DPPH· and OH· in a dose-dependent manner with aqueous extracts of PAR having the highest DPPH· scavenging ability, while extracts from IRV had the highest OH· scavenging ability and inhibition of Fe²⁺-induced MDA production in rat’s pancreas. Furthermore, all the extracts inhibited α-amylase and α-glucosidase activities in a dose-dependent manner. The α-amylase inhibitory effect of MON (IC₅₀ = 0.48 mg/mL) was comparable to that of acarbose (IC₅₀ = 0.40 mg/mL), while the α-glucosidase inhibitory effect of AFZ (IC₅₀ = 0.45 mg/mL) was comparable to that of acarbose (IC₅₀ = 0.39 mg/mL). The results suggest the potential use of the seeds in the dietary management of blood glucose levels associated with type 2 diabetes.