Supplementary MaterialsAdditional file 1 Supplemental Box S1 List of applied exclusion criteria. pharmacodynamic (PD) parameters calculated from pre-meal/dose-adjusted (Pma) serum Apo B-100 values on day 28 . Supplemental Table S7 Summary of statistical comparisons between Flumazenil treatments of postprandial pharmacodynamic (PD) parameters calculated from pre-meal/dose-adjusted (Pma) serum Apo C-III values on day 28. Supplemental Table S8 Summary of median fasting serum lipid concentrations at baseline and after 4?weeks by treatment . Supplemental Table S9 Summary of statistical comparisons of baseline-adjusted Flumazenil fasting lipid concentrations between treatments. Supplemental Figure Flumazenil S1 Mean (standard deviation) unadjusted postprandial triglyceride concentration over time. Supplemental Figure S2 Mean (standard deviation) unadjusted postprandial free fatty acid concentration versus time. Supplemental Figure S3 Mean (standard deviation) unadjusted postprandial Apo A-I concentration versus time. Supplemental Figure S4 Mean (standard deviation) unadjusted postprandial Apo B-48 concentration versus time. Supplemental Figure S5 Mean (standard deviation) unadjusted postprandial Apo B-100 concentration versus time. Supplemental Figure S6 Mean (standard deviation) unadjusted postprandial Apo C-III concentration versus time. 12944_2020_1295_MOESM1_ESM.docx (675K) GUID:?EA069C0E-764B-43B7-9445-A7A145CB566A Data Availability StatementThe datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request. Abstract Background Omega-3 fatty acids (OM3-FAs) are recommended with a low-fat diet for severe hypertriglyceridemia (SHTG), to reduce triglycerides and acute pancreatitis (AP) risk. A low-fat diet may reduce pancreatic lipase secretion, which is required to absorb OM3-ethyl esters (OM3-EEs), but not OM3-carboxylic acids (OM3-CAs). Methods In this exploratory, randomized, open-label, crossover study, 15 Flumazenil patients with SHTG and previous AP were instructed to take OM3-CA (2?g or 4?g) and OM3-EE 4?g once daily for 4?weeks, while adhering to a low-fat diet. On day 28 of each treatment phase, a single dose was administered in the clinic with a liquid low-fat meal, to assess 24-h plasma exposure. Geometric least-squares mean ratios were used for between-treatment comparisons of baseline (day 0)-adjusted area under the plasma concentration versus time curves (AUC0C24) and maximum plasma concentrations (values. Isolated postprandial treatment effects on TG, FFA and apolipoprotein concentrations (pre-meal/dose-adjusted AUC0C24 [Pma-AUC0C24] and (%)standard deviation OM3-FA exposure Mean fasting plasma EPA?+?DHA concentrations (nmol/mL) for the pre-dose samples (??1.5, ??0.75 and???0.25?h) taken at the baseline visits (day 0 of Treatment I [study week 0] and Treatment II [study week 8]; Fig.?1) were 723 (SD, 465) for OM3-CA 2?g, 465 (SD, 305) for OM3-CA 4?g and 522 (SD, 260) for OM3-EE 4?g remedies (Fig.?2). After 4?weeks (day time 28) of dosing even though on a low-fat diet plan, mean pre-dose, fasting (pre-meal [valuevalueconfidence period, coefficient of variation, docosahexaenoic acid, eicosapentaenoic acid, baseline-adjusted area under the plasma concentration versus time curve, from time 0 to 24?h after the start of the meal, Cmax baseline-adjusted maximum measured plasma concentration over the time span specified, omega-3 carboxylic acids, omega-3 ethyl esters, pharmacokinetics, = 14a)high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, omega-3 carboxylic acids, omega-3 ethyl esters, standard deviation, total cholesterol, triglyceride, very-low-density lipoprotein cholesterol Viscosity measures Measurements of fibrinogen (mean baseline value: 10.88?mol/L; SD: 3.69) and blood viscosity under high-shear (mean baseline value: 3.89?cP; SD: 0.75) and low-shear (mean baseline value: 11.79?cP; SD: 11.79) conditions were available in 14 patients. No statistically significant changes from baseline were observed for these variables, including when hematocrit levels were normalized to 45% for the blood viscosity analyses (data not shown). Protection and tolerability AE prices were low general and similar for many Rabbit Polyclonal to Collagen III three remedies (Desk?4). No significant differences in medical laboratory parameters had been observed. Many treatment-emergent AEs had been mild in intensity, and no significant AEs or fatalities from AEs happened. Diarrhea (reported by four individuals) was the just drug-related AE reported by several patient. One discontinuation occurred because of an AE of anemia in an individual having a history background of bone tissue marrow transplant; the anemia was gentle.