scholarly journals A Novel Amorphous Curcumin Preparation Improved Oral Absorption Efficiency in Healthy Volunteers: A Single-Dose, Double-Blind, Two-Way Crossover Study

2020 ◽  
Author(s):  
Yoichi Sunagawa ◽  
Yusuke Miyazaki ◽  
Masafumi Funamoto ◽  
Kana Shimizu ◽  
Satoshi Shimizu ◽  
...  
Keyword(s):  
Single Dose ◽  
Plasma Concentration ◽  
Crossover Study ◽  
Healthy Volunteers ◽  
Oral Absorption ◽  
Biological Activities ◽  
Absorption Efficiency ◽  
Amorphous Solid Dispersion ◽  
Maximum Plasma ◽  
Double Blind

Abstract Background: Curcumin has diverse biological activities such as anti-cancer, antioxidant, and anti-inflammatory properties and is assumed to exhibit beneficial effects in the prevention and treatment of various diseases. Although curcumin is known to be safe in humans, its therapeutic efficacy is limited owing to its poor bioavailability. To overcome this problem, we prepared a novel curcumin preparation curcuRougeTM using the amorphous solid dispersion method. In this study, we aimed to investigate the oral absorption efficiency of curcuRougeTM and compare its efficiency with that of Theracurmin®, a highly absorptive curcumin preparation dispersed with colloidal submicron-particles exhibiting improved bioavailability, in rats and healthy volunteers. Methods: In the animal experiment, male Sprague–Dawley rats were orally administered curcuRougeTM or Theracurmin® (10 mg/kg of curcumin). The plasma curcumin levels were measured at 0.25, 0.5, 1, 2, 4, and 6 h after administration. In addition, we performed a single-dose, double-blind, two-way crossover study to compare plasma curcumin levels after the administration of curcuRougeTM or Theracurmin® in humans. Twelve healthy volunteers were administered curcuRougeTM or Theracurmin® containing 30 mg curcumin. The plasma curcumin concentrations at 0.5, 1, 2, 4, and 8 h after ingestion were determined. Results: The area under plasma concentration–time curve (AUC0-6 h) and maximum plasma concentration (Cmax) of curcuRougeTM in rats were 3.7- and 9.6-fold higher than those of Theracurmin®, respectively. Twelve healthy volunteers were orally administered 90 mg of curcuRougeTM or Theracurmin® in a randomized double-blind crossover study. In these volunteers, the AUC0-8 h and Cmax of curcuRougeTM were 3.4-fold and 5.4-fold higher than those of Theracurmin®, respectively. Conclusion: These findings indicate that curcuRougeTM shows better bioavailability than other highly absorptive curcumin preparations, such as Theracurmin®. Hence, curcuRougeTM is assumed to exhibit clinical efficacy for managing various diseases at a low dose.Trial registration: The trial was registered with the UMIN Clinical Trials Registry (January 8, 2020, UMIN000039083, https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000044573).

Bioavailability of Three Commercial Preparations of Ibuprofen 600 mg

1988 ◽  
Vol 16 (1) ◽  
pp. 44-49 ◽  
Author(s):  
E. Källström ◽  
M. Heikinheimo ◽  
H. Quiding
Keyword(s):  
Single Dose ◽  
Plasma Concentration ◽  
Crossover Study ◽  
Healthy Volunteers ◽  
Plasma Concentrations ◽  
Analgesic Efficacy ◽  
Relative Bioavailability ◽  
Maximum Plasma ◽  
The Mean ◽  
Extent Of Absorption

The pharmacokinetic variables of ibuprofen 600 mg were investigated after administration of Brufen and compared to administration of Burana and Ibumetin. The investigation was carried out as a randomized single-dose crossover study in 17 healthy volunteers. The mean maximum plasma concentrations of ibuprofen were 58, 45 and 54 μg/ml after administration of Brufen, Burana and Ibumetin, respectively, the time to reach this being 1.4, 2.1 and 1.6 h, respectively, after administration. The differences between Brufen and Burana were significant. The relative bioavailability was very similar between Brufen and Burana but about 8% lower for Ibumetin and this difference between Brufen and Ibumetin was significant. Thus, different brands of ibuprofen may not be pharmacokinetically interchangeable and the results show that Brufen is superior to either Burana or Ibumetin when considering both the rate and extent of absorption. These findings are clinically interesting since a high and early plasma concentration of ibuprofen seems to be related to increased analgesic efficacy.

A large multicenter, randomized, double-blind, crossover study in healthy volunteers, comparing pharmacokinetics and pharmacodynamics of Sandoz proposed biosimilar pegfilgrastim with European and United States reference pegfilgrastim.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e23118-e23118
Author(s):  
Gordon P. Otto ◽  
Roumen Nakov ◽  
Steven Schussler ◽  
Stefanie Schier-Mumzhiu ◽  
Celine Schelcher ◽  
...  
Keyword(s):  
Single Dose ◽  
Phase I ◽  
Crossover Study ◽  
Healthy Volunteers ◽  
Phase I Study ◽  
Geometric Mean ◽  
Primary Objective ◽  
Local Tolerability ◽  
Pivotal Phase ◽  
Double Blind

e23118 Background: Similarity of the pharmacokinetic (PK)/pharmacodynamic (PD) profiles of Sandoz proposed biosimilar pegfilgrastim and EU-reference biologic was confirmed in a pivotal Phase I study. In order to confirm PK/PD similarity to the US reference biologic, and to bridge between the two references, a 3-way study was conducted. Methods: A randomized, double-blind, single-dose, 3-treatment, 6-sequence crossover Phase I study was performed in healthy volunteers (HVs) to demonstrate similarity in PK, PD, safety and immunogenicity between Sandoz proposed biosimilar, US reference, and EU reference pegfilgrastim administered subcutaneously (6 mg/0.6 mL) in each treatment period. The primary objective was to demonstrate PK (AUC0-inf, AUC0-last, Cmax) and PD similarity (ANC AUEC0-last, ANC Emax). The study was powered (90%) to achieve confidence intervals (CIs) within biosimilarity margins 0.8─1.25 in pairwise comparisons. Secondary objectives were additional PK/PD parameters, safety and immunogenicity. Results: The study included 577 male and female HVs. PK and PD similarity were demonstrated between Sandoz proposed biosimilar and US reference (Table), as well as EU reference and between both reference biologics since the 90% CIs of the geometric mean ratios were contained within the pre-defined margins of 0.80‒1.25. Safety, immunogenicity and secondary PK/PD parameters were also similar across treatment groups. Conclusions: This large randomized, double-blind, single-dose, 3-treatment, 6-sequence crossover study demonstrated PK and PD similarity between Sandoz proposed biosimilar, US reference and EU reference pegfilgrastim with similar safety, local tolerability and immunogenicity. Clinical trial information: 2016-003549-27. [Table: see text]

scholarly journals A novel amorphous preparation improved curcumin bioavailability in healthy volunteers: A single-dose, double-blind, two-way crossover study

2021 ◽  
Vol 81 ◽  
pp. 104443
Author(s):  
Yoichi Sunagawa ◽  
Yusuke Miyazaki ◽  
Masafumi Funamoto ◽  
Kana Shimizu ◽  
Satoshi Shimizu ◽  
...  
Keyword(s):  
Single Dose ◽  
Crossover Study ◽  
Healthy Volunteers ◽  
Double Blind

scholarly journals Drinkable Preparation of Theracurmin Exhibits High Absorption Efficiency—A Single-Dose, Double-Blind, 4-Way Crossover Study

2013 ◽  
Vol 36 (11) ◽  
pp. 1708-1714 ◽  
Author(s):  
Tatsuya Morimoto ◽  
Yoichi Sunagawa ◽  
Yasufumi Katanasaka ◽  
Sae Hirano ◽  
Masatoshi Namiki ◽  
...  
Keyword(s):  
Single Dose ◽  
Crossover Study ◽  
Absorption Efficiency ◽  
Double Blind ◽  
High Absorption

A single-dose comparative bioavailability study of dronabinol oral solution versus dronabinol capsules in healthy volunteers.

2016 ◽  
Vol 34 (26_suppl) ◽  
pp. 198-198
Author(s):  
Christina Cognata Smith ◽  
Neha Parikh ◽  
William G. Kramer ◽  
Varun Khurana ◽  
Santosh Vetticaden
Keyword(s):  
Single Dose ◽  
Plasma Concentration ◽  
Healthy Volunteers ◽  
Oral Solution ◽  
Individual Variability ◽  
Pharmacokinetic Data ◽  
Maximum Plasma ◽  
Inadequate Response ◽  
Solution Versus ◽  
Time Zero

198 Background: The capsule formulation of dronabinol, a pharmaceutical tetrahydrocannabinol (THC), is approved for anorexia associated with weight loss in patients with AIDS and for cancer chemotherapy-associated nausea/vomiting in patients with inadequate response to conventional antiemetics. A new oral formulation (i.e., dronabinol solution) was evaluated in a bioequivalence study versus currently marketed dronabinol capsules. Methods: In an open-label, 2-treatment, 2-sequence, 4-period, single-dose crossover study, healthy volunteers were randomized to receive 1 of 2 treatment sequences (T-R-T-R or R-T-R-T; T = dronabinol 4.25 mg oral solution and R = dronabinol 5 mg capsules). Dosing occurred after an overnight fast, with a minimum 7-day washout period between treatment periods. A validated liquid chromatography-tandem mass spectrometry method was used to determine plasma concentrations of dronabinol and the primary metabolite 11-OH-Δ9-THC. Results: Fifty-one of 52 enrollees had pharmacokinetic data for analysis. Mean pharmacokinetics were (oral solution vs capsule): Cmax (2.0 vs 2.4 ng/mL), median Tmax (1.0 vs 1.5 h), AUC0-∞ (3.8 vs 4.1 h∙ng/mL), and t1/2 (5.6 vs 3.1 h). The 2 formulations were bioequivalent with respect to maximum plasma concentration (Cmax; reference-scaled criteria) and area under the plasma concentration-time curve (from time zero to last measurable concentration and from time zero to infinity [AUC0-∞]; average bioequivalence) of dronabinol. The data for the 11-OH-Δ9-THC metabolite provide further support for the bioequivalence of the 2 products. Post hoc analysis demonstrated that all volunteers (100%) had detectable plasma dronabinol concentrations at 15 min with the oral solution compared with < 25% of volunteers for the capsules. Intra-individual variability was lower with oral solution versus capsules (for AUC0-∞, 13.5% vs 36.8%, respectively). Conclusions: Dronabinol oral solution 4.25 mg was bioequivalent to dronabinol capsules 5 mg, and exhibited quicker onset of detectable levels and lower intra-individual variability in comparison with dronabinol capsules 5 mg. Clinical trial information: NCT01448772.

A Randomized, Double‐Blind, Single‐Dose, Crossover Study to Demonstrate the Bioequivalence of 2 Formulations of Albiglutide in Healthy Adult Participants

2018 ◽  
Vol 8 (3) ◽  
pp. 361-370 ◽  
Author(s):  
Bonnie C. Shaddinger ◽  
Georgios Vlasakakis ◽  
Joseph Soffer ◽  
Karl M. Thorpe ◽  
Daniel Hatch ◽  
...  
Keyword(s):  
Single Dose ◽  
Crossover Study ◽  
Healthy Adult ◽  
Double Blind ◽  
Adult Participants

An Evaluation of the Antihistamine Activity of Acrivastine and Its Onset in Human Skin

1992 ◽  
Vol 20 (2) ◽  
pp. 106-111 ◽  
Author(s):  
V K Manna ◽  
P Marks ◽  
J R Gibson
Keyword(s):  
Crossover Study ◽  
Healthy Volunteers ◽  
Human Skin ◽  
Treatment Plan ◽  
Onset Of Action ◽  
Double Blind ◽  
Time Points ◽  
Antihistamine Activity ◽  
Flare Response ◽  
Histamine Challenge

In a double-blind, two-period crossover study, 24 healthy volunteers were evaluated to establish the time of onset of action of activity of acrivastine in suppressing the weal and flare response to intradermally injected histamine. Volunteers received single doses of 8 mg acrivastine and placebo according to a fully randomized, balanced treatment plan. Acrivastine significantly ( P < 0.002) reduced the flare response induced by 0.4 μg histamine challenge 15 min after oral acrivastine dosing when compared with placebo. A significant ( P < 0.001) reduction of the weal response was noted at 25 min, although trends in this direction were already present at earlier time points. Dans d'une étude croisée à deux phase, réalisée en double aveugle et ayant porté sur 24 volontaires sains, on a tenté d'établir le moment du début de l'action de l'acrivastine dans la suppression de la réponse inflammatoire consécutive à l'injection intradermique d'histamine. Les volontaires ont reçu des doses uniques de 8 mg d'acrivastine et de placebo, selon un plan de traitement entièrement randomisé et équilibré. L'acrivastine a réduit significativement ( P < 0,002) la réponse de rubéfaction induite par 0,4 μg d'histamine 15 minutes après l'administration orale d'acrivastine, par rapport au placebo. Une réduction significative ( P < 0,001) de la réponse d'enflure a été notée à 25 minutes, bien qu'une tendance en ce sens ait déjà été observée à un stade plus précoce.

Abstract 2009: ALX-0081 a Novel Anti-Thrombotic: Results of a Single-Dose Phase 1 Study in Healthy Volunteers and Further Development in Patients with Stable Angina Undergoing PCI

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Jozef Bartunek ◽  
Emanuele Barbato ◽  
Josefin-Beate Holz ◽  
Kristof Vercruysse ◽  
Hans Ulrichts ◽  
...  
Keyword(s):  
Single Dose ◽  
Healthy Volunteers ◽  
Dose Escalation ◽  
Stable Angina ◽  
Thrombus Formation ◽  
Phase 1 ◽  
Controlled Study ◽  
Double Blind ◽  
Phase Ib ◽  
Wide Range

Background : ALX-0081 is a bivalent Nanobody ® based on the variable domain of naturally occurring heavy-chain only antibodies. It binds with high affinity to the A1 domain of von Willebrand Factor (vWF) and thereby blocks the interactions between platelets and vascular collagen. It selectively prevents thrombus formation under high shear stress conditions. Aim : Test ALX-0081 single IV infusions (60 minutes) dosed from 0.5mg to 12mg total in 40 male healthy volunteers in double-blind, randomized, placebo controlled study and assess pharmacokinetic (PK), pharmacodynamic (PD), safety and immunogenicity. Results : ALX-0081 displayed non-linear pharmacokinetic properties, following a 2 compartment model. Ristocetin induced platelet aggregation (RIPA) was analyzed as marker for PD effect with full inhibition (defined as measured levels dropping <10%) observed at ALX-0081 concentrations of ~ 400ng/ml. All subjects dosed ≥ 2mg achieved full RIPA inhibition at 1h post-dosing for maximum of 12h. ALX-0081 treatment was well tolerated and safe, no signs of bleeding were reported and no immunogenic response was detected. Target related mild and transient reductions of vWF and FVIII plasma levels were observed and all events were fully reversible. Phase Ib study design : double-blind, randomized, placebo controlled, multiple ascending dose study. ALX-0081 added to standard anti-thrombotic regimen (ASA, clopidogrel, UFH) in patients with stable angina undergoing elective PCI. Single-dose escalation will be followed by multiple dosing (up to 4 doses in 24h). Dose escalation will be guided by safety and efficacy marker. Endpoints: safety, pharmacological profile, biomarker (RIPA, RICO and ACT) and early clinical outcome (MACE, IMR, molecular marker). Conclusion : ALX-0081 can be administered safely over a wide range of dose-regimen. First results of the phase Ib study in stable angina patients will be presented.

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