Pharmacokinetics and pharmacodynamics of HTD1801 (berberine ursodeoxycholate, BUDCA) in patients with hyperlipidemia

Autor: Philip Lavin, Adrian M. Di Bisceglie, Meng Yu, Gerald F. Watts, Ru Bai, Liping Liu
Jazyk: angličtina
Rok vydání: 2020
Předmět:
Adult
Male
medicine.medical_specialty
Berberine
Endocrinology
Diabetes and Metabolism
Clinical Biochemistry
Hypercholesterolemia
Hyperlipidemias
Coronary Artery Disease
030204 cardiovascular system & hematology
Gastroenterology
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
Endocrinology
Ezetimibe
Internal medicine
Hyperlipidemia
medicine
Diabetes Mellitus
Humans
Pharmacokinetics
lcsh:RC620-627
Aged
Triglyceride
Dose-Response Relationship
Drug
Cholesterol
business.industry
Research
Biochemistry (medical)
Ursodeoxycholate
Cholesterol
LDL
Middle Aged
medicine.disease
Dose-ranging study
lcsh:Nutritional diseases. Deficiency diseases
chemistry
Tolerability
Ursodeoxycholic acid
030220 oncology & carcinogenesis
Female
lipids (amino acids
peptides
and proteins)
Hydroxymethylglutaryl-CoA Reductase Inhibitors
business
medicine.drug
Lipoprotein
Zdroj: Lipids in Health and Disease, Vol 19, Iss 1, Pp 1-10 (2020)
Lipids in Health and Disease
Popis: Background Reduction in elevated serum cholesterol concentrations is important in the management of individuals at risk of atherosclerotic cardiovascular disease (ASCVD), such as myocardial infarction and thrombotic stroke. Although HMGCoA reductase inhibitors (“statins”) are frequently used for this purpose, a significant proportion of patients remain at increased residual risk of ASCVD as they do not adequately address some of the associated co-morbidities such as diabetes and fatty liver disease. Methods A double-blind, randomized, placebo-controlled, dose ranging study was carried out that compared three doses of berberine ursodeoxycholate (BUDCA) to placebo in a cohort of subjects with a history of hypercholesterolemia and serum LDL cholesterol levels above 2.59 mmol/L (> 99.9 mg/dL). BUDCA was administered in two divided doses each day for 28 days. The primary endpoints of the study were safety and tolerability of this new compound, as well as its effect in lowering serum lipid and lipoprotein concentrations. Results A total of 50 subjects were enrolled into three dose cohorts in this study. BUDCA was generally well tolerated, even at doses of 2000 mg per day (the highest dose group); there were no significant adverse effects reported and this highest dose was associated with significant reductions in LDL cholesterol. By day 28 and with the highest dose of BUDCA, there were significant reductions in the serum concentrations of total cholesterol by 8.2% (P = 0.0004) and LDL cholesterol by 10.4% (P = 0.0006), but no significant changes in triglyceride and HDL cholesterol concentrations. Conclusions BUDCA is a new single molecular entity that has a significant but modest effect in safely lowering serum LDL-cholesterol concentrations in individuals with a history of hypercholesterolemia. It has a potential use for treating hypercholesterolemia in individuals who cannot take statins, and possibly as adjunctive to other agents, such as ezetimibe or bempedoic acid. Trial registration The study was registered on Clinicaltrials.gov (NCT03381287).
Databáze: OpenAIRE
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