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.

Effect of food on the pharmacokinetics of dronabinol oral solution versus dronabinol capsules in healthy volunteers.

2016 ◽  
Vol 34 (26_suppl) ◽  
pp. 199-199
Author(s):  
Christina Cognata Smith ◽  
D. Alexander Oh ◽  
Neha Parikh ◽  
Varun Khurana ◽  
Santosh Vetticaden
Keyword(s):  
Healthy Volunteers ◽  
Therapeutic Benefit ◽  
Oral Solution ◽  
Individual Variability ◽  
Pharmacokinetic Data ◽  
Inadequate Response ◽  
Open Label ◽  
Post Dose ◽  
Solution Versus ◽  
Fed State

199 Background: Dronabinol, a pharmaceutical tetrahydrocannabinol (THC), capsule is approved for anorexia associated with weight loss in patients with AIDS and for cancer chemotherapy-induced nausea/vomiting in patients with inadequate response to conventional antiemetic therapy. Food effects on absorption and bioavailability of a new dronabinol oral solution was compared with marketed capsules. Methods: In an open-label, single-dose, 3-period crossover study, healthy volunteers were randomized to receive dronabinol oral solution 4.25 mg (fed) or dronabinol capsule 5 mg (fed or fasted), after a 7-day washout period. Doses were administered under a fasted (overnight) or fed state (high-fat/calorie meal 30 minutes pre-dose). Plasma pharmacokinetics was evaluated for dronabinol and the major metabolite, 11-OH-Δ9-THC. Results: Pharmacokinetic data of 54 volunteers were analyzed. In the fed state, initial dronabinol absorption was rapid with oral solution versus capsules (mean Tlag, 0.15 vs 2.02 h), and 100% and 15% of volunteers receiving oral solution and capsules, respectively, had detectable plasma dronabinol levels 30 minutes post-dose. Inter-individual variability in plasma dronabinol concentrations during early absorption was less with oral dronabinol solution (%CV: 82.79%, 83.94%, and 90.68%) versus capsules (%CV: 318.54%, 250.33%, and 182.01%) observed at 0.5, 1, and 2 h, respectively, after dosing. Food increased mean AUC0-t similarly for dronabinol oral solution and capsules, versus capsules with fasting, increasing exposure to oral solution and capsules 2.1- to 2.4-fold. Mean Tmax was similarly delayed for dronabinol oral solution (7.7 h) and capsules (5.6 h) with food relative to fasting (1.7 h). On the basis of 11-OH-Δ9-THC plasma levels, AUC0-t up to 48 h postdose and AUC0-inf were found to be similar for the oral solution and capsules under fed conditions. Conclusions: An appreciable food effect was observed for dronabinol oral solution and capsules. Dronabinol oral solution may offer therapeutic benefit to patients given its rapid absorption and lower inter-individual variability compared with dronabinol capsules. Clinical trial information: NCT01448772.

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).

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

2016 ◽  
Vol 34 (15_suppl) ◽  
pp. e21595-e21595
Author(s):  
Neha Parikh ◽  
William G. Kramer ◽  
Varun Khurana ◽  
Christina Cognata Smith ◽  
Santosh Vetticaden
Keyword(s):  
Single Dose ◽  
Healthy Volunteers ◽  
Oral Solution ◽  
Solution Versus ◽  
Bioavailability Study ◽  
Comparative Bioavailability ◽  
Comparative Bioavailability Study

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.

scholarly journals Bioavailability study of dronabinol oral solution versus dronabinol capsules in healthy volunteers

2016 ◽  
Vol Volume 8 ◽  
pp. 155-162
Author(s):  
Neha Parikh ◽  
William Kramer ◽  
Varun Khurana ◽  
Christina Cognata Smith ◽  
Santosh Vetticaden
Keyword(s):  
Healthy Volunteers ◽  
Oral Solution ◽  
Solution Versus ◽  
Bioavailability Study

scholarly journals Single-Dose Safety, Tolerability, and Pharmacokinetics of the Antibiotic GSK1322322, a Novel Peptide Deformylase Inhibitor

2013 ◽  
Vol 57 (5) ◽  
pp. 2005-2009 ◽  
Author(s):  
Odin J. Naderer ◽  
Etienne Dumont ◽  
John Zhu ◽  
Milena Kurtinecz ◽  
Lori S. Jones
Keyword(s):  
Single Dose ◽  
Plasma Concentration ◽  
Dose Escalation ◽  
Peptide Deformylase ◽  
Maximum Plasma ◽  
High Fat ◽  
Content Type ◽  
Atypical Pathogens ◽  
Fat Meal ◽  
Dose Proportional

ABSTRACTGSK1322322 is a potent inhibitor of peptide deformylase, an essential bacterial enzyme required for protein maturation. GSK1322322 is active against community-acquired skin and respiratory tract pathogens, including methicillin-resistantStaphylococcus aureus, multidrug-resistantStreptococcus pneumoniae, and atypical pathogens. This phase I, randomized, double-blind, placebo-controlled, 2-part, single-dose, dose escalation study (first time in humans) evaluated the safety, tolerability, and pharmacokinetics of GSK1322322 (powder-in-bottle formulation) in healthy volunteers. In part A, dose escalation included GSK1322322 doses of 100, 200, 400, 800, and 1,500 mg under fasting conditions and 800 mg administered with a high-fat meal. In part B, higher doses of GSK1322322 (2,000, 3,000, and 4,000 mg) were evaluated under fasting conditions. Of the 39 volunteers enrolled in the study, 29 and 10 volunteers were treated with GSK1322322 and placebo, respectively. Upon single-dose administration, GSK1322322 was absorbed rapidly, with median times to maximum plasma concentration (Tmax) ranging from 0.5 to 1.0 h. The maximum observed plasma concentration (Cmax) and exposure (area under the concentration-time curve [AUC]) of GSK1322322 were greater than dose proportional between 100 and 1,500 mg and less than dose proportional between 1,500 and 4,000 mg. Administration of the drug with a high-fat meal reduced the rate of absorption (reducedCmaxand delayedTmax) without affecting the extent of absorption (no effect on AUC). GSK1322322 was generally well tolerated, with all adverse events being mild to moderate in intensity during both parts of the study. The most frequently reported adverse event was headache. Data from this study support further evaluation of GSK1322322.

scholarly journals Enhanced Bioavailability of Itraconazole in Hydroxypropylβ-Cyclodextrin Solution versus Capsules in Healthy Volunteers

1998 ◽  
Vol 42 (7) ◽  
pp. 1862-1865 ◽  
Author(s):  
Joseph A. Barone ◽  
Bruce L. Moskovitz ◽  
Joseph Guarnieri ◽  
Alan E. Hassell ◽  
John L. Colaizzi ◽  
...  
Keyword(s):  
Crossover Study ◽  
Healthy Volunteers ◽  
Oral Solution ◽  
Solution Versus ◽  
Male Volunteers ◽  
The Times

ABSTRACT The bioavailabilities and bioequivalences of single 200-mg doses of itraconazole solution and two capsule formulations were evaluated in a crossover study of 30 male volunteers. The two capsule formulations were bioequivalent. The bioavailabilities of the solutions itraconazole and hydroxyitraconazole were 30 to 33% and 35 to 37% greater, respectively, than those of either capsule. However, the maximum concentrations of the drug in plasma (C max), the times to C max, and the terminal half-lives were comparable for all three formulations. These data indicate that the bioavailabilities of itraconazole and hydroxyitraconazole are enhanced when administered as an oral solution instead of capsules.

scholarly journals Multiple-Dose Safety, Tolerability, and Pharmacokinetics of Oral Nemonoxacin (TG-873870) in Healthy Volunteers

2010 ◽  
Vol 54 (1) ◽  
pp. 411-417 ◽  
Author(s):  
David T. Chung ◽  
Cheng-Yuan Tsai ◽  
Shu-Jen Chen ◽  
Li-Wen Chang ◽  
Chi-Hsin R. King ◽  
...  
Keyword(s):  
Plasma Concentration ◽  
Healthy Volunteers ◽  
Bacterial Infections ◽  
Maximum Plasma Concentration ◽  
Maximum Plasma ◽  
Time Curve ◽  
Once Daily ◽  
Concentration Time ◽  
Atypical Pathogens ◽  
Plasma Concentration Time Curve

ABSTRACT Nemonoxacin (TG-873870) is a novel nonfluorinated quinolone with broad-spectrum activities against Gram-positive and Gram-negative aerobic, anaerobic, and atypical pathogens, as well as against methicillin-resistant Staphylococcus aureus, vancomycin-resistant S. aureus, and multiple-resistant bacterial pathogens. We conducted a randomized, double-blind, placebo-controlled, dose-escalating study to ascertain the safety, tolerability, and pharmacokinetics of nemonoxacin. We enrolled 46 healthy volunteers and used a once-daily oral-dosing range of 75 to 1,000 mg for 10 days. Additionally, the food effect was evaluated in subjects in the 500-mg cohort. Nemonoxacin was generally safe and well tolerated, with no significant changes in the clinical laboratory tests or electrocardiograms. Adverse effects, including headache, contact dermatitis, and rash, were mild and resolved spontaneously. Nemonoxacin was rapidly absorbed within 2 h postdosing, and generally, a steady state was reached after 3 days. The maximum plasma concentration and the area under the plasma concentration-time curve were dose proportional over the dosing range. The elimination half-life was approximately 7.5 h and 19.7 h on days 1 and 10, respectively. Approximately 37 to 58% of the drug was excreted in the urine. Food affected the pharmacokinetics, with decreases in the maximum plasma concentration and area under the plasma concentration-time curve of 46% and 27%, respectively. However, the free AUC/MIC90 of nemonoxacin was more than 100 under both the fasting and fed conditions, predicting the efficacy of nemonoxacin against most of the tested pathogens. In conclusion, the results support further clinical investigation of once-daily nemonoxacin administration for antibiotic-sensitive and antibiotic-resistant bacterial infections.

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