dihydropyridines and Anemia

dihydropyridines has been researched along with Anemia* in 4 studies

Trials

1 trial(s) available for dihydropyridines and Anemia

ArticleYear
Novel Compound Induces Erythropoietin Secretion through Liver Effects in Chronic Kidney Disease Patients and Healthy Volunteers.
    American journal of nephrology, 2018, Volume: 48, Issue:3

    TP0463518 is a novel hypoxia-inducible factor prolyl hydroxylase inhibitor developed to aid in the treatment of anemia associated with chronic kidney disease (CKD) and is expected to increase erythropoietin (EPO) derived from liver. Two phase I studies were conducted in healthy volunteers (HV) and CKD patients undergoing hemodialysis (i.e., HD patients) or those not undergoing dialysis (i.e., ND patients).. Pharmacokinetics, pharmacodynamics, and safety profiles of TP0463518 were assessed. Forty HV received single oral doses of TP0463518 at 3, 6, 11, 20, and 36 mg or placebo. Twenty ND patients received single doses of TP0463518 at 1, 6, and 11 mg and 9 HD patients received TP0463518 at 1 and 11 mg doses. To identify the source organ of EPO, glycosylation patterns were determined using percentage migrated isoform (PMI) values.. Declining renal function slowed elimination of TP0463518 and increased the mean AUC0-∞. ∆Emax of serum EPO in 11-mg groups of HV, ND patients, and HD patients were 24.37 ± 11.37, 201.57 ± 130.34, and 1,324.76 ± 1,189.24 mIU/mL respectively. A strong correlation was -observed between logarithm conversions of ∆Emax and AUC0-∞ with correlation coefficients of 0.945. PMI values of blood after TP0463518 administration were elevated to similar or higher levels in comparison with those of umbilical cord blood, which mainly contains liver-derived EPO.. TP0463518 induced dose-dependent EPO production, mainly derived from the liver in HV and CKD patients. These results suggest that TP0463518 is a new strategy for treating anemia in CKD, which can be used regardless of renal functions.

    Topics: Administration, Oral; Adult; Aged; Anemia; Area Under Curve; Dihydropyridines; Dose-Response Relationship, Drug; Erythropoietin; Female; Glomerular Filtration Rate; Healthy Volunteers; Humans; Hypoxia-Inducible Factor-Proline Dioxygenases; Kidney; Liver; Male; Middle Aged; Pyridines; Renal Dialysis; Renal Insufficiency, Chronic; Treatment Outcome; Young Adult

2018

Other Studies

3 other study(ies) available for dihydropyridines and Anemia

ArticleYear
TP0463518 (TS-143) Ameliorates Peptidoglycan-Polysaccharide Induced Anemia of Inflammation in Rats.
    Biological & pharmaceutical bulletin, 2021, Volume: 44, Issue:11

    TP0463518 (TS-143) is a competitive prolyl hydroxylase 1/2/3 pan-inhibitor, and has been shown to specifically stabilize hypoxia-inducible factor-2 alpha in the liver to increase erythropoietin production. While TP0463518 has been shown to improve renal anemia, its effect on anemia of inflammation is still unknown. In this study, we created a rat model of anemia of inflammation by administering peptidoglycan-polysaccharide (PG-PS) to Lewis rats; the PG-PS-treated rats developed anemia within 2 weeks after the PG-PS challenge. The hematopoietic effects of oral TP0463518 administration at 10 mg/kg once daily for 6 weeks were examined in this rat model. The hematocrit values in the TP0463518-treated group increased significantly from 32.8 ± 0.8 to 44.5 ± 2.1% after the treatment, which was comparable to that in the healthy control group. The change of the mean corpuscular volume following TP0463518 treatment was similar to that in the healthy control group up to week 4, and significantly higher than that in the vehicle-treated group. TP0463518 increased divalent metal transporter 1 and duodenal cytochrome b expressions in the intestine. Conversely, TP0465318 did not exert any effects on the expressions of genes involved in iron metabolism in the liver, even though TP0463518 dramatically increased erythropoietin expression. Furthermore, TP0463518 had no effect on the expressions of inflammation markers in the liver. These results suggest that TP0463518 increased iron absorption and improved anemia of inflammation without exacerbating liver inflammation. TP0463518 appears to have an acceptable safety profile and could become a useful new therapeutic option for anemia of inflammation.

    Topics: Anemia; Animals; Blotting, Western; Dihydropyridines; Enzyme-Linked Immunosorbent Assay; Female; Inflammation; Iron; Peptidoglycan; Polysaccharides; Prolyl-Hydroxylase Inhibitors; Pyridines; Rats; Rats, Inbred Lew; Transferrin

2021
    Genetic testing and molecular biomarkers, 2021, Volume: 25, Issue:4

    Topics: Adult; Aged; Anemia; Antineoplastic Combined Chemotherapy Protocols; Biomarkers, Pharmacological; Biomarkers, Tumor; Colorectal Neoplasms; Dihydropyridines; Dihydrouracil Dehydrogenase (NADP); Disease-Free Survival; Female; Fluorouracil; Humans; Male; Middle Aged; Oxidoreductases; Polymorphism, Single Nucleotide; Prognosis; Turkey

2021
TP0463518, a novel inhibitor for hypoxia-inducible factor prolyl hydroxylases, increases erythropoietin in rodents and monkeys with a good pharmacokinetics-pharmacodynamics correlation.
    European journal of pharmacology, 2018, Nov-05, Volume: 838

    Topics: Anemia; Animals; Dihydropyridines; Disease Models, Animal; Enzyme Assays; Enzyme Inhibitors; Erythropoietin; Hematinics; Humans; Hypoxia-Inducible Factor 1, alpha Subunit; Hypoxia-Inducible Factor-Proline Dioxygenases; Inhibitory Concentration 50; Macaca fascicularis; Mice; Mice, Inbred BALB C; Pyridines; Rats; Rats, Sprague-Dawley; Renal Insufficiency, Chronic

2018