scholarly journals Trans-Resveratrol Oral Bioavailability in Humans Using LipiSperse™ Dispersion Technology

Pharmaceutics ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 1190
Author(s):  
David Briskey ◽  
Amanda Rao
Keyword(s):  
Single Dose ◽  
Oral Bioavailability ◽  
Maximum Concentration ◽  
Randomized Study ◽  
Venous Blood ◽  
Area Under The Curve ◽  
Fold Increase ◽  
Double Blind ◽  
Potential Health ◽  
Liquid Chromatography Tandem Mass

Resveratrol is a naturally produced compound that has been well researched for its potential health benefits. The primary hindrance towards resveratrol’s therapeutic efficacy is its traditionally poor oral bioavailability. LipiSperse® is a novel delivery system designed to increase the dispersion of lipophilic ingredients, like resveratrol, in aqueous environments. This single-dose, double-blind, randomized study compared the pharmacokinetics of a commercially available resveratrol with (Veri-Sperse®) and without (Veri-te) the LipiSperse® delivery complex. Healthy adults randomly received a single dose of either 150 Veri-te, 75 Veri-Sperse®, or 150 mg Veri-Sperse®. Venous blood samples were taken prior to dosing in a fasted state and at 0.5, 1, 2, 3, 4, 5, 6, 8 and 24 h post supplementation. Plasma trans-resveratrol conjugates were measured by liquid-chromatography tandem mass spectrometry (LC-MS/MS). The area under the curve (AUC) (0–24 h), maximum concentration (Cmax), and time of maximum concentration (Tmax) of plasma conjugates were calculated. The 150 mg dose of Veri-Sperse® had a 2-fold increase in absorption (AUC) and a 3-fold increase in Cmax of trans-resveratrol conjugates compared to 150 mg Veri-te. There was no statistical difference between 75 Veri-Sperse and 150 mg Veri-te for AUC or Cmax of resveratrol conjugates. These findings provide support for the use of LipiSperse® to improve absorption of resveratrol.

scholarly journals Leukocyte DNA Damage and Wound Infection after Nitrous Oxide Administration

2013 ◽  
Vol 118 (6) ◽  
pp. 1322-1331 ◽  
Author(s):  
Yan Chen ◽  
Xiaodong Liu ◽  
Christopher H. K. Cheng ◽  
Tony Gin ◽  
Kate Leslie ◽  
...  
Keyword(s):  
Dna Damage ◽  
Nitrous Oxide ◽  
Wound Infection ◽  
Controlled Trial ◽  
Venous Blood ◽  
Fold Increase ◽  
Postoperative Wound Infection ◽  
Double Blind ◽  
Postoperative Wound ◽  
Oxygen Groups

Abstract Background: Nitrous oxide inactivates methionine synthase and may lead to DNA damage and wound infection. By using single-cell gel electrophoresis (comet assay), the authors determined the effect of nitrous oxide on DNA damage in circulating leukocytes. Methods: In this double-blind, randomized controlled trial, 91 patients undergoing major colorectal surgery were randomized to receive 70% nitrous oxide (n = 31) or nitrous oxide-free anesthesia using 30 (n = 30) or 80% (n = 30) oxygen. Venous blood was collected before and 24 h after surgery. The primary outcome was extent of DNA damage, quantified as the percentage of DNA staining intensity in the comet tail using digital fluorescence microscopy. Incidence of postoperative wound infection was also recorded. Results: Nitrous oxide exposure was associated with a two-fold increase in the percentage of DNA intensity in tail (P = 0.0003), but not in the 30 (P = 0.181) or 80% oxygen groups (P = 0.419). There was a positive correlation between the duration of nitrous oxide exposure and extent of DNA damage, r = 0.33, P = 0.029. However, no correlation was observed in nitrous oxide-free patients. The proportions of postoperative wound infection, using the Centers for Disease Control and Prevention criteria, were 19.4% (6 of 31) in the 70% nitrous oxide group and 6.7% (2 of 30) in both the 30 and 80% oxygen groups, P = 0.21. An increase in DNA damage was associated with a higher risk of wound infection, adjusted odds ratio (95% CIs): 1.19 (1.07–1.34), P = 0.003. Conclusions: Nitrous oxide increased DNA damage compared with nitrous oxide-free anesthesia and was associated with postoperative wound infection.

scholarly journals PHARMACOKINETIC STUDIES OF A CHRONOTHERAPEUTIC DRUG DELIVERY SYSTEM OF LORNOXICAM BY LC-MS/MS METHOD

2018 ◽  
Vol 10 (6) ◽  
pp. 88
Author(s):  
Sindhu Abraham ◽  
Rajamanickam Deveswaran ◽  
Jayaraman Anbu ◽  
Sharon Furtado ◽  
Bharath Srinivasan
Keyword(s):  
Drug Delivery ◽  
Drug Release ◽  
Maximum Concentration ◽  
Area Under The Curve ◽  
Immediate Release ◽  
Pharmacokinetic Parameters ◽  
Pharmacokinetic Studies ◽  
Elimination Half ◽  
Coated Tablet ◽  
Liquid Chromatography Tandem Mass

Objective: The objective of this study was to investigate differences in pharmacokinetic patterns of immediate release tablet (IR) and compression coated tablet (CCT) of lornoxicam, proposed for the chronotherapeutic treatment of rheumatoid arthritis.Methods: The dosage forms were administered to two groups of white New Zealand rabbits (n=3), and the plasma drug levels were measured by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Pharmacokinetic parameters like maximum concentration (Cmax), time is taken to reach maximum concentration (Tmax), area under the curve (AUC), elimination half-life (t1/2) and Mean Residence Time (MRT) were determined.Results: In the case of IR tablets, the drug was detected within 15 min after oral administration and a Cmax of 1269.57±4.04 ng/ml were attained at 2±0.15 h. With CCT, the drug was detected only after 5 h and a Cmax of 1279.24±12.76 ng/ml were attained at 8±0.10 h. The CCT showed maximum drug release at the eighth hour in comparison to IR tablet which showed maximum release at the second hour of study.Conclusion: The predominant lag time prior to drug release from CCT is an indication that it is consistent with the requirements of chronopharmaceutical drug delivery. The results suggest that the compression coated tablet is a promising approach for chronotherapeutic management of rheumatoid arthritis.

Comparative study of the effects of zopiclone (7.5 mg), zolpidem, flunitrazepam and a placebo on nocturnal cognitive performance in healthy subjects, in relation to pharmacokinetics

1995 ◽  
Vol 10 (S3) ◽  
pp. 129s-135s ◽  
Author(s):  
H Allain ◽  
A Patat ◽  
A Lieury ◽  
F Le Coz ◽  
C Janus ◽  
...  
Keyword(s):  
Single Dose ◽  
Visual Analogue Scale ◽  
Cognitive Performance ◽  
Healthy Subjects ◽  
Analogue Scale ◽  
Randomized Study ◽  
Residual Effect ◽  
Pharmacodynamic Effect ◽  
Double Blind ◽  
Nocturnal Period

SummaryThe effect of zopiclone (7.5 mg) on attention, vigilance and memory components was evaluated during a nocturnal period in comparison to a placebo, to zolpidem (10 mg) and to flunitrazepam (1 mg) in a double blind, randomized study, after administration of a single dose in 16 young healthy volunteers. It appears that there is a clear effect on attention and vigilance; this effect is apparent during the kinetic phase of the absorption of the medication. The effect on memory is transient and is absent four hours after the ingestion of the drug. The objective results are not strictly consistent with the chronology of the subjective parameters (Leeds scale — Visual Analogue Scale). The three hypnotics under comparison do not fundamentally differ except in their kinetic/pharmacodynamic effect relationship. One important fact, taking the parameters as a whole, is that there is no objective “residual” effect.

scholarly journals Bioequivalence of levamlodipine besylate tablets in healthy Chinese subjects: A single-dose and two-period crossover randomized study

2020 ◽  
Author(s):  
Li Xin ◽  
Chenjing Wang ◽  
Ting Li ◽  
Yanping Liu ◽  
Shuqin Liu ◽  
...  
Keyword(s):  
Single Dose ◽  
Randomized Study ◽  
Plasma Concentrations ◽  
Bioequivalence Study ◽  
Pharmacokinetic Parameters ◽  
Open Label ◽  
Liquid Chromatography Tandem Mass ◽  
The Mean ◽  
Healthy Chinese ◽  
Chinese Subjects

Abstract Background: Levamlodipine, a calcium channel blocker, has been show act as a cardiovascular drug. To compare the pharmacokinetic parameters between levamlodipine (test formulation) at a single dose of 5 mg and amlodipine (reference formulation) at a single dose of 10 mg, the bioequivalence study was carried out.Methods: A single-dose randomized, open-label, two-period crossover study was designed in healthy Chinese subjects. 48 subjects were divided into fasted and fed groups equally. The subjects randomly received the test or reference formulations at the rate of 1:1. Following a 21-day washout period, the alternative formulations were received. The blood samples were collected at 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 14, 24, 36, 48, 72, 96, 120, 144, 168 hours later. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) was applied to determine the plasma concentrations of levamlodipine. Adverse events were recorded.Results: The 90% confidence intervals (CIs) of the ratio of geometric means (GMRs) of Cmax, AUC0-t, and AUC0-∞ under both fasted and fed conditions were within the prespecified bioequivalence limits between 80~125%. Under fasted conditions, 24 subjects were enrolled and completed the study. The mean Cmax was (2.70±0.49) ng/mL, AUC0-t was (141.32±36.24) ng×h/mL and AUC0-∞ was (157.14±45.65) ng×h/mL after a single dose of 5 mg levamlodipine. The mean Cmax was (2.83±0.52) ng/mL, AUC0-t was (153.62±33.96) ng×h/mL and AUC0-∞ was (173.05±41.78) ng×h/mL after a single dose of 10 mg amlodipine. Under fed conditions, 24 subjects were enrolled and completed the study. The mean Cmax was (2.73±0.55) ng/mL, AUC0-t was (166.93±49.96) ng×h/mL and AUC0-∞ was (190.99±70.89) ng×h/mL after a single dose of 5 mg levamlodipine. The mean Cmax was (2.87±0.81) ng/mL AUC0-t was (165.46±43.58) ng×h/mL and AUC0-∞ was (189.51±64.70) ng×h/mL after a single dose of 10 mg amlodipine. Serious adverse event was not observed.Conclusion: The trial confirmed that levamlodipine at a single dose of 5 mg and amlodipine at a single dose of 10 mg were bioequivalent under both fasted condition and fed condition.Trial registration: Cinicaltrials, NCT04411875. Registered 3 June 2020 - Retrospectively registered, https://register.clinicaltrials.gov/prs/app/action/SelectProtocol?sid=S0009W1Q&selectaction=Edit&uid=U00050YQ&ts=3&cx=-6iqkm8

scholarly journals Absorption Kinetics of Berberine and Dihydroberberine and Their Impact on Glycemia: A Randomized, Controlled, Crossover Pilot Trial

Nutrients ◽  
2021 ◽  
Vol 14 (1) ◽  
pp. 124
Author(s):  
Jessica M. Moon ◽  
Kayla M. Ratliff ◽  
Anthony M. Hagele ◽  
Richard A. Stecker ◽  
Petey W. Mumford ◽  
...  
Keyword(s):  
Standardized Test ◽  
Venous Blood ◽  
Pilot Trial ◽  
Area Under The Curve ◽  
Preliminary Evidence ◽  
Crossover Fashion ◽  
Double Blind ◽  
Fourth Dose ◽  
Study Participants ◽  
The Impact

Berberine is a natural alkaloid used to improve glycemia but displays poor bioavailability and increased rates of gastrointestinal distress at higher doses. Recently, dihydroberberine has been developed to combat these challenges. This study was designed to determine the rate and extent to which berberine appeared in human plasma after oral ingestion of a 500 mg dose of berberine (B500) or 100 mg and 200 mg doses of dihydroberberine (D100 and D200). In a randomized, double-blind, crossover fashion, five males (26 ± 2.6 years; 184.2 ± 11.6 cm; 91.8 ± 10.1 kg; 17.1 ± 3.5% fat) completed a four-dose supplementation protocol of placebo (PLA), B500, D100, and D200. The day prior to their scheduled visit, participants ingested three separate doses with breakfast, lunch, and dinner. Participants fasted overnight (8–10 h) and consumed their fourth dose with a standardized test meal (30 g glucose solution, 3 slices white bread) after arrival. Venous blood samples were collected 0, 20, 40, 60, 90, and 120 minutes (min) after ingestion and analyzed for BBR, glucose, and insulin. Peak concentration (CMax) and area under the curve (AUC) were calculated for all variables. Baseline berberine levels were different between groups (p = 0.006), with pairwise comparisons indicating that baseline levels of PLA and B500 were different than D100. Berberine CMax tended to be different (p = 0.06) between all conditions. Specifically, the observed CMax for D100 (3.76 ± 1.4 ng/mL) was different than PLA (0.22 ± 0.18 ng/mL, p = 0.005) and B500 (0.4 ± 0.17 ng/mL, p = 0.005). CMax for D200 (12.0 ± 10.1 ng/mL) tended (p = 0.06) to be different than B500. No difference in CMax was found between D100 and D200 (p = 0.11). Significant differences in berberine AUC were found between D100 (284.4 ± 115.9 ng/mL × 120 min) and PLA (20.2 ± 16.2 ng/mL × 120 min, p = 0.007) and between D100 and B500 (42.3 ± 17.6 ng/mL × 120 min, p = 0.04). Significant differences in D100 BBR AUC (284.4 ± 115.9 ng/mL×120 min) were found between PLA (20.2 ± 16.2 ng/mL × 120 min, p = 0.042) and B500 (42.3 ± 17.6 ng/mL × 120 min, p = 0.045). Berberine AUC values between D100 and D200 tended (p = 0.073) to be different. No significant differences in the levels of glucose (p = 0.97) and insulin (p = 0.24) were observed across the study protocol. These results provide preliminary evidence that four doses of a 100 mg dose of dihydroberberine and 200 mg dose of dihydroberberine produce significantly greater concentrations of plasma berberine across of two-hour measurement window when compared to a 500 mg dose of berberine or a placebo. The lack of observed changes in glucose and insulin were likely due to the short duration of supplementation and insulin responsive nature of study participants. Follow-up efficacy studies on glucose and insulin changes should be completed to assess the impact of berberine and dihydroberberine supplementation in overweight, glucose intolerant populations.

scholarly journals Benefits of dexamethasone use in thyroid surgery: A prospective, randomized study

2020 ◽  
Vol 148 (9-10) ◽  
pp. 565-570
Author(s):  
Dragana Radovanovic ◽  
Sanja Milosev ◽  
Zoran Radovanovic ◽  
Svetlana Skoric-Jokic ◽  
Silvija Lucic ◽  
...  
Keyword(s):  
Single Dose ◽  
Thyroid Surgery ◽  
Randomized Study ◽  
Postoperative Nausea And Vomiting ◽  
Double Blind Study ◽  
Nacl Solution ◽  
Double Blind ◽  
Time Period ◽  
Group A ◽  
Group B

Introduction/Objective. This study aimed to investigate the effects of preoperative dexamethasone use on the incidence and severity of postoperative nausea and vomiting (PONV), postsurgical pain, and vocal impairment after thyroid surgery. Methods. We performed a prospective, randomized, double-blind study with 50 patients who underwent thyroid surgery. Group A patients (n = 25) received 0.9% NaCl solution (2 ml) before anesthesia, patients in Group B (n = 25) were administered 8 mg of dexamethasone. All the patients preoperatively received 4 mg of ondansetron. During the first 48 hours after surgery, postoperative complications were monitored in defined periods. Results. PONV rate and severity was significantly lower in Group B than in Group A (p < 0.05). Patients in Group B reported less pain in resting and in activity (p < 0.05) and lower vocal impairment (p < 0.05) than patients in Group A in each defined time period. Conclusion. Preoperatively adding dexamethasone to ondansetron is more effective than use of ondansetron alone in the prevention of PONV. Dexamethasone significantly reduces the pain and improves voice function; therefore, we could advise routine single-dose dexamethasone use before thyroid surgery.

scholarly journals Bioequivalence of levamlodipine besylate tablets in healthy Chinese subjects: A single-dose and two-period crossover randomized study

2020 ◽  
Author(s):  
Li Xin ◽  
Chenjing Wang ◽  
Ting Li ◽  
Yanping Liu ◽  
Shuqin Liu ◽  
...  
Keyword(s):  
Single Dose ◽  
Randomized Study ◽  
Plasma Concentrations ◽  
Bioequivalence Study ◽  
Pharmacokinetic Parameters ◽  
Open Label ◽  
Liquid Chromatography Tandem Mass ◽  
The Mean ◽  
Healthy Chinese ◽  
Chinese Subjects

Abstract Background: Levamlodipine, a calcium channel blocker, has been show act as a cardiovascular drug. To compare the pharmacokinetic parameters between levamlodipine (test formulation) at a single dose of 5 mg and amlodipine (reference formulation) at a single dose of 10 mg, the bioequivalence study was carried out.Methods: A single-dose randomized, open-label, two-period crossover study was designed in healthy Chinese subjects. 48 subjects were divided into fasted and fed groups equally. The subjects randomly received the test or reference formulations at the rate of 1:1. Following a 21-day washout period, the alternative formulations were received. The blood samples were collected at 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 14, 24, 36, 48, 72, 96, 120, 144, 168 hours later. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) was applied to determine the plasma concentrations of levamlodipine. Adverse events were recorded.Results: The 90% confidence intervals (CIs) of the ratio of geometric means (GMRs) of Cmax, AUC0-t, and AUC0-∞ under both fasted and fed conditions were within the prespecified bioequivalence limits between 80~125%. Under fasted conditions, 24 subjects were enrolled and completed the study. The mean Cmax was (2.70±0.49) ng/mL, AUC0-t was (141.32±36.24) ng×h/mL and AUC0-∞ was (157.14±45.65) ng×h/mL after a single dose of 5 mg levamlodipine. The mean Cmax was (2.83±0.52) ng/mL, AUC0-t was (153.62±33.96) ng×h/mL and AUC0-∞ was (173.05±41.78) ng×h/mL after a single dose of 10 mg amlodipine. Under fed conditions, 24 subjects were enrolled and completed the study. The mean Cmax was (2.73±0.55) ng/mL, AUC0-t was (166.93±49.96) ng×h/mL and AUC0-∞ was (190.99±70.89) ng×h/mL after a single dose of 5 mg levamlodipine. The mean Cmax was (2.87±0.81) ng/mL AUC0-t was (165.46±43.58) ng×h/mL and AUC0-∞ was (189.51±64.70) ng×h/mL after a single dose of 10 mg amlodipine. Serious adverse event was not observed.Conclusion: The trial confirmed that levamlodipine at a single dose of 5 mg and amlodipine at a single dose of 10 mg were bioequivalent under both fasted condition and fed condition.Trial registration: Cinicaltrials, NCT04411875. Registered 3 June 2020 - Retrospectively registered, https://register.clinicaltrials.gov/prs/app/action/SelectProtocol?sid=S0009W1Q&selectaction=Edit&uid=U00050YQ&ts=3&cx=-6iqkm8

scholarly journals A First-in-Human Randomized, Double-Blind, Placebo-Controlled, Single- and Multiple-Ascending Oral Dose Study of Novel Imidazolopiperazine KAF156 To Assess Its Safety, Tolerability, and Pharmacokinetics in Healthy Adult Volunteers

2014 ◽  
Vol 58 (11) ◽  
pp. 6437-6443 ◽  
Author(s):  
F. Joel Leong ◽  
Rong Zhao ◽  
Shuqi Zeng ◽  
Baldur Magnusson ◽  
Thierry T. Diagana ◽  
...  
Keyword(s):  
Single Dose ◽  
Adverse Events ◽  
Oral Dose ◽  
Maximum Concentration ◽  
Food Effect ◽  
Renal Elimination ◽  
Pharmacokinetic Data ◽  
Upper Respiratory Tract ◽  
Double Blind ◽  
Dose Study

ABSTRACTKAF156 belongs to a new class of antimalarial, the imidazolopiperazines, and is currently in clinical development for the treatment of uncomplicated malaria. This first-in-human, single- and multiple-ascending-dose study in 70 healthy male volunteers determined the maximum oral dose of KAF156 tolerated by healthy adults and derived pharmacokinetic data (including preliminary food effect) to enable dose calculations for malaria patients. KAF156 was studied in single-dose cohorts (10 to 1,200 mg, including one 400-mg food effect cohort (4 to 10 subjects/cohort), and in multiple-dose cohorts (60 to 600 mg once daily for 3 days; 8 subjects/cohort). The follow-up period was 6 to 14 days after the last dose. KAF156 was tolerated, with self-limited mild to moderate gastrointestinal and neurological adverse events. In treated subjects after single doses, headache (n= 4; 11.1%), diarrhea (n= 3; 8.3%), dizziness (n= 3; 8.3%), and abdominal pain (n= 2; 5.6%) were the most common adverse events. Headache (n= 4; 16.7%), nausea (n= 3; 12.5%), upper respiratory tract infection (n= 3; 12.5%), and dizziness (n= 2; 8.3%) were the most common adverse events following multiple doses. KAF156 time to maximum concentration (Tmax) was between 1.0 and 6.0 h. Both the area under the concentration-time curve (AUC) and maximum concentration (Cmax) increased more than dose-proportionally in both single- and multiple-ascending-dose cohorts (terminal half-life, 42.5 to 70.7 h). There was no significant accumulation over 3-day repeated administration. The extent of absorption was not significantly affected by food at a single dose of 400 mg, while meanCmaxdecreased from 778 ng/ml to 627 ng/ml andTmaxwas delayed from a median of 3.0 h under fasting conditions to 6.0 h under fed conditions. Renal elimination is a minor route.

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