scholarly journals Pharmacokinetic and pharmacodynamic similarity between SAR341402 insulin aspart and Japan-approved NovoRapid in healthy Japanese subjects

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Masanari Shiramoto ◽  
Tatsuya Yoshihara ◽  
Wolfgang Schmider ◽  
Hiroki Takagi ◽  
Irene Nowotny ◽  
...  
Keyword(s):  
Insulin Aspart ◽  
Plasma Insulin ◽  
Maximum Plasma ◽  
Plasma Insulin Concentration ◽  
Double Blind ◽  
Time Curve ◽  
Glucose Levels ◽  
Blood Glucose Levels ◽  
Primary Endpoints ◽  
Quantifiable Concentration

AbstractThis study compared the pharmacokinetic and glucodynamic profiles of biosimilar SAR341402 insulin aspart to Japan-approved insulin aspart (NovoRapid) in healthy Japanese males. In this single-center, randomized, double-blind, single-dose, two-period, crossover study, subjects received 0.3 U/kg of SAR341402 or NovoRapid before undergoing a 10 h euglycemic clamp procedure. Plasma insulin aspart concentrations and blood glucose levels were measured, and glucose infusion rates (GIRs) were assessed. Primary endpoints were maximum plasma insulin aspart concentration (INS-Cmax), area under the plasma insulin concentration–time curve to the last quantifiable concentration (INS-AUClast), area under the GIR–time curve during the clamp (GIR-AUC0–10 h), and maximum GIR (GIRmax). Forty subjects were randomized with 39 completing both treatment periods. Pharmacokinetic exposure showed a mean ratio between products of 1.00 (90% confidence interval [CI] 0.94–1.05) for INS-Cmax and 1.02 (90% CI 1.00–1.04) for INS-AUClast. Glucodynamic activity showed a mean ratio between products of 1.00 (95% CI 0.93–1.06) for GIR-AUC0–10 h and 1.01 (95% CI 0.95–1.08) for GIRmax. The 90% CIs for pairwise treatment ratios were within the predefined equivalence range of 0.80–1.25. Both treatments were well tolerated. We concluded that similar pharmacokinetic exposure and glucodynamic potency were shown for SAR341402 and NovoRapid in healthy Japanese males.

Food intake rather than blood glucose levels affects the pharmacokinetic profile of insulin aspart in pigs

2021 ◽  
Author(s):  
Anna Katrina Jógvansdóttir Gradel ◽  
Jonas Kildegaard ◽  
Trine Porsgaard ◽  
Jens Lykkesfeldt ◽  
Hanne Hoffman Frølund Refsgaard
Keyword(s):  
Blood Glucose ◽  
Food Intake ◽  
Insulin Aspart ◽  
Pharmacokinetic Profile ◽  
Glucose Levels ◽  
Blood Glucose Levels

scholarly journals L-Dopa Pharmacokinetic Profile with Effervescent Melevodopa/Carbidopa versus Standard-Release Levodopa/Carbidopa Tablets in Parkinson’s Disease: A Randomised Study

2015 ◽  
Vol 2015 ◽  
pp. 1-7 ◽  
Author(s):  
Fabrizio Stocchi ◽  
Laura Vacca ◽  
Paola Grassini ◽  
Stephen Pawsey ◽  
Holly Whale ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Plasma Concentration ◽  
Pharmacokinetic Profile ◽  
Pharmacokinetic Parameters ◽  
Maximum Plasma ◽  
Double Blind ◽  
Time Curve ◽  
Randomised Study ◽  
Effervescent Tablet

Objectives.To characterize the pharmacokinetic profile of levodopa (L-dopa) and carbidopa after repeated doses of the effervescent tablet of melevodopa/carbidopa (V1512; Sirio) compared with standard-release L-dopa/carbidopa in patients with fluctuating Parkinson’s disease. Few studies assessed the pharmacokinetics of carbidopa to date.Methods.This was a single-centre, randomized, double-blind, double-dummy, two-period crossover study. Patients received V1512 (melevodopa 100 mg/carbidopa 25 mg) or L-dopa 100 mg/carbidopa 25 mg, 7 doses over 24 hours (Cohort 1), 4 doses over 12 hours (Cohort 2), or 2 doses over 12 hours in combination with entacapone 200 mg (Cohort 3). Pharmacokinetic parameters included area under the plasma-concentration time curve (AUC), maximum plasma concentration (Cmax), and time toCmax(tmax).Results.Twenty-five patients received at least one dose of study medication. L-dopa absorption tended to be quicker and pharmacokinetic parameters less variable after V1512 versus L-dopa/carbidopa, both over time and between patients. Accumulation of L-dopa in plasma was less noticeable with V1512. Carbidopa exposure and interpatient variability was lower when V1512 or L-dopa/carbidopa was given in combination with entacapone. Both treatments were well tolerated.Conclusions.V1512 provides a more reliable L-dopa pharmacokinetic profile versus standard-release L-dopa/carbidopa, with less drug accumulation and less variability. This trial is registered with ClinicalTrials.govNCT00491998.

scholarly journals Mulberry leaf extract improves glycaemic response and insulaemic response to sucrose in healthy subjects: results of a randomized, double blind, placebo-controlled study

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Pariyarath Sangeetha Thondre ◽  
Helen Lightowler ◽  
Lis Ahlstrom ◽  
Andrew Gallagher
Keyword(s):  
Blood Glucose ◽  
Leaf Extract ◽  
Lifestyle Changes ◽  
Glycaemic Response ◽  
Double Blind ◽  
Glucose Levels ◽  
Mulberry Leaf ◽  
Blood Glucose Levels ◽  
Mulberry Leaf Extract ◽  
White Mulberry

Abstract Background There are many benefits of maintaining healthy blood glucose levels, and studies have shown that lifestyle changes such as changes to diet can successfully restore normoglycaemia in participants with dysglycaemia. Significant health-related lifestyle changes are often difficult to implement and functional ingredients that can reduce glycaemic and insulaemic responses may help at risk populations. The aim of this study was to investigate whether a mulberry leaf extract could lower the glycaemic and insulinaemic responses to 75 g sucrose in healthy individuals. Methods A double-blind, randomised, placebo-controlled, crossover design trial was conducted by the Oxford Brookes Centre for Nutrition and Health. Thirty-eight participants were recruited into the trial and, after an overnight fast, were given 75 g sucrose + white mulberry leaf extract, or 75 g sucrose alone. Capillary blood samples were collected at 15-min intervals in the first hour and at 30-min intervals over the second hour to determine glucose and plasma insulin levels. Data analysis was conducted using a paired samples T test or a Wilcoxon signed rank test. Results The addition of mulberry leaf extract to sucrose resulted in a significantly lower glycaemic response and insulinaemic response compared to a matched placebo (sucrose alone). The change in blood glucose measurements were significantly lower at 15 min (p < 0.001), 30 min (p < 0.001), 45 min (p = 0.008), and 120 min (p < 0.001) and plasma insulin measurements were significantly lower at 15 min (p < 0.001), 30 min (p < 0.001), 45 min (p < 0.001), 60 min (p = 0.001) and 120 min (p < 0.001). The glucose iAUC (− 42%, p = 0.001), insulin iAUC (− 40%, p < 0.001), peak glucose (− 40.0%, p < 0.001) and peak insulin (− 41%, p < 0.001) from baseline were significantly lower for white mulberry leaf extract compared with the placebo. White mulberry leaf extract was well tolerated and there were no reported adverse events. Conclusions Mulberry leaf extract can be used as part of lifestyle changes that may lead to healthy blood glucose levels. Trial registration: ISRCTN99601810 (23 October 2020, retrospectively registered)

scholarly journals Glucose metabolism and incretins level in morbidly obese patients and in patients after biliopancreatic diversion performed for morbid obesity

2014 ◽  
Vol 11 (1) ◽  
pp. 24-31
Author(s):  
I I Dedov ◽  
G A Melnichenko ◽  
E A Troshina ◽  
N V Mazurina ◽  
N A Ogneva ◽  
...  
Keyword(s):  
Blood Glucose ◽  
Glucose Metabolism ◽  
Biliopancreatic Diversion ◽  
Plasma Insulin ◽  
Fasting Glucose ◽  
Morbidly Obese ◽  
Obese Patients ◽  
Insulin Levels ◽  
Glucose Levels ◽  
Blood Glucose Levels

We’ve studied a carbohydrate metabolism in morbidly obese (MO) patients and the patients after bariatric surgery. The patients of the 1st group had BMI40 (n=22) and no history of diabetes mellitus. Patients after biliopancreatic diversion (BPD) performed for MO were included in the 2nd group (n=23). The 3rd group was a control group of normal weight healthy subjects (n=22). Blood glucose levels, insulin, GLP-1, GIP and glucagon during the OGTT (with 75 g of glucose) at 0, 30, 60 and 120 minutes were measured in all patients. In MO group fasting glucose levels were the highest. Impaired glucose metabolism was revealed in 68.2% of patients (n=10). Impaired fasting glucose (IFG) was diagnosed in 4 cases (18.2%), impaired glucose tolerance (IGT) in 11 patients (50%). In the BPD postprandial blood glucose levels (120 min) were lower if compared to the other groups. In 4 individuals (17.4%) we found postprandial hypoglycemia (2.8 mmol/l). Patients of the MO group had the highest fasting insulin levels and HOMA-IR (p0.001). The maximum of insulin concentration was seen on minute 30 of the OGTT in the 2nd and 3rd groups, and it was significantly higher in the post-bariatric patients (p=0.026). In MO group the maximum of the plasma insulin levels were on the 60th minute and were still elevated after 120 minutes. Fasting and stimulated (on the 30th minute) levels of GLP-1 were significantly higher after BPD (р=0.037 and p=0.022 at 0 and 30 min, respectively). Morbidly obese patients had higher fasting and stimulated GIP. Fasting glucagon concentrations were similar in the surgical and control groups, while the people with MO had higher initial levels of glucagon (p=0.013) and it was not suppressed during the OGTT (p=0.076). Glucose intolerance and insulin resistance incidence was higher in MO patients. Hyperglucagonemia, increased GIP and decreased GLP-1 levels are observed in MO patients. Stimulated plasma insulin and GLP-1 concentrations were significantly increased in patients who underwent BPD, and may cause postprandial hypoglycemia.

scholarly journals The Impact of Re-Mating Interval and Genotype on Physiological Response of Rabbits after First Kindling

2021 ◽  
Vol 16 (1) ◽  
pp. 1
Author(s):  
Shereen S. Ghoneim ◽  
Sawsan A. Nasr ◽  
I. El-Wardany ◽  
A. Farid ◽  
A. H. Ahmed ◽  
...  
Keyword(s):  
Plasma Glucose ◽  
Plasma Insulin ◽  
Tail Length ◽  
Hormone Concentration ◽  
Plasma Insulin Concentration ◽  
Plasma Urea ◽  
Glucose Levels ◽  
Mating Interval ◽  
Plasma Leptin ◽  
The Impact

This is an experiment aimed to study the effect of re-mating interval on rabbit does after first kindling on hormonal (insulin, leptin, and T3) and metabolites (triglycerides, urea, and glucose) levels. DNA damage in ovary cells of rabbit does during the 2nd parity was also studied. Two varieties were used: APRI (synthetic line) and Baladi Black (BB, Egyptian breed). A total number of 120 mature rabbit does (60 does for each breed) were 6 months of age and were used at the beginning of the breeding season. Does of each breed were divided into three equal groups according to reproductive rhythm. The 1st group was postpartum (PP). The 2nd group was 11 days after parturition (P11). The 3rd group was post-weaning (PW). There were significant (P&ge;0.05) differences in plasma leptin concentration during 1st parity. The highest value of plasma leptin concentration was recorded by the PW group at mating. Also, there were significant differences in plasma insulin and T3 hormones concentrations of doe rabbits. The highest value of plasma insulin concentration was recorded by the PW group at mating in 1st parity and the highest value of plasma T3 hormone concentration was recorded for the PS group at mating. While there were insignificant differences during 2nd parity in T3 hormone concentration in rabbits, the differences of plasma glucose and triglyceride concentrations of doe rabbits during 1st parity and 2nd parity were significant. However, the highest significant value of plasma glucose concentration was recorded by the PW group at mating. On the other hand, there were insignificant differences in plasma urea concentration of doe rabbits during 1st parity and 2nd parity. Finally, no significant effects were observed on comet length, head diameter, tail length, or DNA % tail.

Pharmacokinetics, safety and tolerability of ravidasvir, with and without danoprevir/ritonavir, in healthy subjects

2021 ◽  
Author(s):  
Guolan Wu ◽  
Huili Zhou ◽  
Jing Wu ◽  
Duo Lv ◽  
Lihua Wu ◽  
...  
Keyword(s):  
Steady State ◽  
Plasma Concentration ◽  
Fold Increase ◽  
Sequential Design ◽  
Maximum Plasma ◽  
Double Blind ◽  
Time Curve ◽  
Once Daily ◽  
Concentration Time ◽  
Multiple Doses

Ravidasvir (RDV) is a novel oral hepatitis C virus NS5A inhibitor. This study aimed to evaluate the pharmacokinetics and safety of RDV and the drug–drug interaction between RDV and ritonavir-boosted danoprevir (DNVr) in healthy adults. In 1 st study, healthy volunteers were administered oral single doses of 100, 200 and 300 mg RDV and 200 mg once daily for 7 days. The 2 nd study was randomized, double-blind and placebo-controlled sequential design (day 1 for 200 mg RDV alone, day 7 for 100 mg/100 mg DNVr, day 13 for 200 mg RDV plus 100mg/100mg DNVr, followed by RDV 200 mg once daily with DNVr 100mg/100mg twice daily for 10 days). The results showed that RDV exposure increased in a dose-proportional manner following a single dose with no evidence of accumulation with multiple doses. Co-administration with DNVr regimen (100 mg/100 mg, twice daily) resulted in a 2.92- and 1.99-fold increase in minimum plasma concentration at steady state (C min,ss ) and area under the concentration–time curve at steady state (AUC τ ) of RDV. With co-administration of RDV, maximum plasma concentration (C max ) and area under the concentration curve from zero to 12 h (AUC 0-12 ) of DNV increased 1.71-fold and 2.33-fold, respectively. We did not observe any significant changes in ritonavir exposure. Both single and multiple doses of RDV with or without DNVr were well tolerated. The favorable pharmacokinetic and safety results support ravidasvir’s continued clinical development and treatment.

scholarly journals A phase I, randomized, single-dose pharmacokinetic study comparing sb8 (bevacizumab biosimilar) with reference bevacizumab in healthy volunteers

2020 ◽  
Vol 86 (4) ◽  
pp. 567-575 ◽  
Author(s):  
Donghoon Shin ◽  
Yoon Jung Lee ◽  
Jihye Choi ◽  
Dahyoung Lee ◽  
Minjeong Park ◽  
...  
Keyword(s):  
Single Dose ◽  
Adverse Events ◽  
Healthy Volunteers ◽  
Neutralizing Antibodies ◽  
Study Drug ◽  
The European Union ◽  
Double Blind ◽  
Time Curve ◽  
Single Dose Study ◽  
Primary Endpoints

Abstract Purpose To compare pharmacokinetics, safety, tolerability, and immunogenicity between SB8, a bevacizumab biosimilar, and the European Union (EU) and United States (US) reference products (bevacizumab-EU, bevacizumab-US). Methods In this randomized, double-blind, parallel-group, and single-dose study, healthy volunteers were randomized to receive a 3 mg/kg dose of SB8, bevacizumab-EU, or bevacizumab-US via intravenous infusion. Primary endpoints were area under the concentration–time curve from time zero to infinity (AUCinf) and to the last quantifiable concentration (AUClast), and maximum observed serum concentration (Cmax). Bioequivalence was achieved if 90% confidence intervals (CIs) for the ratios of the geometric least squares means (LSMeans) of primary endpoints were within the predefined bioequivalence margins of 80.00–125.00%. Safety and immunogenicity were also investigated. Results The 90% CIs for the geometric LSMean ratios of AUCinf, AUClast and Cmax were all within the prespecified bioequivalence margins. Geometric LSMean ratios for SB8/bevacizumab-EU, SB8/bevacizumab-US and bevacizumab-EU/bevacizumab-US were 88.01%, 88.48% and 100.54% for AUCinf, 88.65%, 89.08% and 100.49% for AUClast and 99.59%, 101.15% and 101.56% for Cmax, respectively. Incidence of treatment-emergent adverse events (TEAEs) across treatment groups was comparable (SB8: 50.0%, bevacizumab-EU: 37.5%, bevacizumab-US: 53.8%). Most TEAEs were mild and considered as not related to the study drug. No deaths or treatment discontinuations due to adverse events occurred. Incidence of anti-drug antibodies was also comparable between all groups and no neutralizing antibodies were detected. Conclusion This study demonstrated pharmacokinetic bioequivalence and similar safety and immunogenicity profiles of SB8 to both reference products, bevacizumab-EU and bevacizumab-US, and of bevacizumab-EU to bevacizumab-US. Clinicaltrials.gov identifier NCT02453672 (submitted date); EudraCT number: 2015-001,026-41.

scholarly journals Ascorbic Acid-Rich Moringa oleifera Lam. Extract Inhibits Hepatorenal Toxicity and Enhances the Endogenous Antioxidant Levels in Streptozotocin-Induced Type II Diabetes

2019 ◽  
pp. 25-35
Author(s):  
Vikas Kumar ◽  
Ankit Sahoo ◽  
Prakash Khadka ◽  
Deeksha Chauhan ◽  
Azizah Salim Bawadood ◽  
...  
Keyword(s):  
Blood Glucose ◽  
Plasma Insulin ◽  
Moringa Oleifera ◽  
Density Lipoprotein ◽  
Diabetic Rats ◽  
The Body ◽  
Glucose Levels ◽  
Blood Glucose Levels ◽  
Treatment Of Diabetes ◽  
Moringa Oleifera Lam

Background. The cases of diabetes increase day by day due to unhealthy lifestyle, food habit, and less food intake. Novel drugs for the treatment of diabetes are urgently needed. Most researchers are looking for alternative drugs (plant-based drugs) for the treatment of diabetes. Objective. The current experiment was designed to examine the hepatic and renal beneficial effect of Moringa oleifera Lam. (MO) extract in the streptozotocin (STZ)-induced diabetes. Methods. Antidiabetic potential of the MO extract was estimated in terms of blood glucose levels, plasma insulin, hexokinase, and glucose-6-phosphate. Antihyperlipidemic effects of MO extract were evaluated through the estimation of low-density lipoprotein (LDL) cholesterol, total cholesterol (TC), triglyceride (TG), very LDL (VLDL) cholesterol, and high-density lipoprotein (HDL) level whereas the antioxidant effects were evaluated through estimation of catalase (CAT), superoxide dismutase (SOD), malondialdehyde (MDA), and glutathione peroxidase (GPx) levels in diabetic rats. Results. Dose-dependent treatment using MO extract significantly increased the body weight, hexokinase, plasma insulin, HDL, SOD, CAT, and GPx levels (P < 0.001) and significantly decreased the levels of fasting blood glucose, TC, TGs, LDL, VLDL, MDA, fructose-1,6-bisphosphate, glucose-6-phosphate, and glycated hemoglobin in STZ-induced diabetic rats (P < 0.001). Conclusion. MO can be used as a therapeutic agent in the management of elevated blood glucose levels through the alterations in the blood glucose level, plasma level of insulin, and various biochemical parameters.

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