scholarly journals Application of a dermatopharmacokinetic (DPK) method for bioequivalence assessment of topical metronidazole creams

2020 ◽  
Vol 23 ◽  
pp. 437-450
Author(s):  
Seeprarani Rath ◽  
Ashmita Ramanah ◽  
Charles Bon ◽  
Isadore Kanfer
Keyword(s):  
Statistical Power ◽  
Reference Product ◽  
Human Subjects ◽  
Tape Stripping ◽  
Gravimetric Analysis ◽  
Time Duration ◽  
Healthy Human ◽  
Topical Metronidazole ◽  
Negative Controls ◽  
Bioequivalence Assessment

Purpose: The main aim of the current research was to develop and apply a dermatopharmacokinetic (DPK) approach for the bioequivalence assessment of metronidazole (MTZ) topical cream products, indicated in the treatment of rosacea. Methods: A DPK methodology using tape stripping (TS) technique was developed by investigating the factors that may influence the TS results viz. tapes, dose durations, number of tapes to be used, pressure application, dose applied and gravimetric analysis of the tapes. An initial dose duration study was performed on 6 healthy participants to determine an appropriate application time duration using the Emax model. The SC thickness was normalised between participants using TEWL measurements. A pivotal study was conducted using both the arms of 10 healthy human participants to demonstrate the ability of the TS method for bioequivalence assessment by comparing the reference product to itself as a positive control and including products with higher and lower strengths of MTZ to serve as negative controls in order to confirm bioinequivalence. Results: Whereas the reference was found to be bioequivalent when compared to itself, the creams containing 0.56% and 0.95% MTZ (negative controls) were not bioequivalent (bioinequivalent). Furthermore, another product containing 0.75% MTZ was also assessed and was found to be bioequivalent to the reference product. In addition, the use of both forearms of each participant offered an important advantage of significantly reducing the number of human subjects required to demonstrate BE with a high statistical power of > 80%. Conclusion: The data obtained provides compelling evidence that the developed TS method has the potential to be a cost-effective surrogate alternative for lengthy and expensive clinical trials. Consequently, its application can facilitate faster development of generic products which would, in turn, lower the economic burden of healthcare.

scholarly journals Bioequivalence of Topical Clotrimazole Formulations: An Improved Tape Stripping Method

2011 ◽  
Vol 14 (3) ◽  
pp. 347 ◽  
Author(s):  
Natalie Rae Parfitt ◽  
Michael Frederick Skinner ◽  
Charles Bon ◽  
Isadore Kanfer
Keyword(s):  
Reference Product ◽  
Transepidermal Water Loss ◽  
Hplc Method ◽  
Tape Stripping ◽  
Compelling Evidence ◽  
Application Time ◽  
Stripping Method ◽  
Bioequivalence Assessment ◽  
Tape Strip

Purpose: Investigations were carried out to assess the use of tape stripping (TS) for the determination of bioequivalence of topical products containing 1% clotrimazole. Methods: The study design involved the establishment of an appropriate application time, which was determined by conducting a dose duration study. Subsequently, two bioequivalence studies were conducted: i) using the brand (Canesten Topical - 1% clotrimazole cream) as both the test and the reference product and ii) comparing Canesten cream with a gel product containing the same concentration of clotrimazole (1%). Each tape strip was individually analyzed for clotrimazole content using an HPLC method and Transepidermal Water Loss (TEWL) measurements were used to normalize the stratum corneum thicknesses between subjects. Results: The results of the TS investigations showed that, if the study is sufficiently powered, tape stripping may be used to determine bioequivalence according to the conventional bioequivalence limits of 0.8–1.25, as well as detect formulation differences between different clotrimazole products. Conclusions: The data from this study provided compelling evidence that tape stripping has the necessary attributes and potential to be used as a tool for the bioequivalence assessment of topical clotrimazole and/or other topical formulations, thereby circumventing the need to undertake expensive and time-consuming clinical trials for such products. This article is open to POST-PUBLICATION REVIEW. Registered readers (see “For Readers”) may comment by clicking on ABSTRACT on the issue’s contents page.

scholarly journals Pharmacokinetics and bioequivalence assessment of optimized directly compressible Aceclofenac (100 mg) tablet formulation in healthy human subjects

PLoS ONE ◽  
2020 ◽  
Vol 15 (9) ◽  
pp. e0238951
Author(s):  
Rabia Bushra ◽  
Muhammad Harris Shoaib ◽  
Huma Ali ◽  
Sana Ghayas
Keyword(s):  
Human Subjects ◽  
Tablet Formulation ◽  
Healthy Human ◽  
Healthy Human Subjects ◽  
Bioequivalence Assessment

Minimizing Carry-Over Effects After Treatment Failure and Maximizing Therapeutic Outcome

2014 ◽  
Vol 222 (3) ◽  
pp. 171-178 ◽  
Author(s):  
Mareile Hofmann ◽  
Nathalie Wrobel ◽  
Simon Kessner ◽  
Ulrike Bingel
Keyword(s):  
Treatment Failure ◽  
Human Subjects ◽  
Subsequent Treatment ◽  
Clinical Samples ◽  
Administration Route ◽  
Healthy Human ◽  
Negative Experiences ◽  
Analgesic Treatment ◽  
Balanced Design ◽  
Carry Over

According to experimental and clinical evidence, the experiences of previous treatments are carried over to different therapeutic approaches and impair the outcome of subsequent treatments. In this behavioral pilot study we used a change in administration route to investigate whether the effect of prior treatment experience on a subsequent treatment depends on the similarity of both treatments. We experimentally induced positive or negative experiences with a topical analgesic treatment in two groups of healthy human subjects. Subsequently, we compared responses to a second, unrelated and systemic analgesic treatment between both the positive and negative group. We found that there was no difference in the analgesic response to the second treatment between the two groups. Our data indicate that a change in administration route might reduce the influence of treatment history and therefore be a way to reduce negative carry-over effects after treatment failure. Future studies will have to validate these findings in a fully balanced design including larger, clinical samples.

Detection of Soluble Fibrin Monomer Complexes in Blood by Means of Protamine Sulphate Test

1968 ◽  
Vol 20 (01/02) ◽  
pp. 044-049 ◽  
Author(s):  
B Lipiński ◽  
K Worowski
Keyword(s):  
Human Subjects ◽  
Coronary Thrombosis ◽  
Mean Value ◽  
Healthy Human ◽  
Protamine Sulphate ◽  
Soluble Fibrin ◽  
Fibrin Monomer ◽  
Dog Plasma ◽  
The Mean ◽  
Precipitable Protein

SummaryIn the present paper described is a simple test for detecting soluble fibrin monomer complexes (SFMC) in blood. The test consists in mixing 1% protamine sulphate with diluted oxalated plasma or serum and reading the optical density at 6190 Å. In experiments with dog plasma, enriched with soluble fibrin complexes, it was shown that OD read in PS test is proportional to the amount of fibrin recovered from the precipitate. It was found that SFMC level in plasma increases in rabbits infused intravenously with thrombin and decreases after injection of plasmin with streptokinase. In both cases PS precipitable protein in serum is elevated indicating enhanced fibrinolysis. In healthy human subjects the mean value of OD readings in plasma and sera were found to be 0.30 and 0.11, while in patients with coronary thrombosis they are 0.64 and 0.05 respectively. The origin of SFMC in circulation under physiological and pathological conditions is discussed.

Chronic stress decreases circulating endocannabinoid 2-arachidonoylglycerol in healthy human subjects

2015 ◽  
Author(s):  
Buqing Yi ◽  
Igor Nichiporuk ◽  
Matthias Feuerecker ◽  
Gustav Schelling ◽  
Alexander Chouker
Keyword(s):  
Chronic Stress ◽  
Human Subjects ◽  
Healthy Human ◽  
Healthy Human Subjects

scholarly journals Acacia Gum Is Well Tolerated While Increasing Satiety and Lowering Peak Blood Glucose Response in Healthy Human Subjects

Nutrients ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 618
Author(s):  
Riley Larson ◽  
Courtney Nelson ◽  
Renee Korczak ◽  
Holly Willis ◽  
Jennifer Erickson ◽  
...  
Keyword(s):  
Blood Glucose ◽  
Human Subjects ◽  
Area Under The Curve ◽  
Soluble Fiber ◽  
Healthy Human ◽  
Glucose Response ◽  
Blood Glucose Response ◽  
Acacia Gum ◽  
Fiber Treatment ◽  
Healthy Human Subjects

Acacia gum (AG) is a non-viscous soluble fiber that is easily incorporated into beverages and foods. To determine its physiological effects in healthy human subjects, we fed 0, 20, and 40 g of acacia gum in orange juice along with a bagel and cream cheese after a 12 h fast and compared satiety, glycemic response, gastrointestinal tolerance, and food intake among treatments. Subjects (n = 48) reported less hunger and greater fullness at 15 min (p = 0.019 and 0.003, respectively) and 240 min (p = 0.036 and 0.05, respectively) after breakfast with the 40 g fiber treatment. They also reported being more satisfied at 15 min (p = 0.011) and less hungry with the 40 g fiber treatment at 30 min (p = 0.012). Subjects reported more bloating, flatulence, and GI rumbling on the 40 g fiber treatment compared to control, although values for GI tolerance were all low with AG treatment. No significant differences were found in area under the curve (AUC) or change from baseline for blood glucose response, although actual blood glucose with 20 g fiber at 30 min was significantly less than control. Individuals varied greatly in their postprandial glucose response to all treatments. AG improves satiety response and may lower peak glucose response at certain timepoints, and it is well tolerated in healthy human subjects. AG can be added to beverages and foods in doses that can help meet fiber recommendations.

Heart rate variability and baroreflex sensitivity are reduced in chronically undernourished, but otherwise healthy, human subjects

2003 ◽  
Vol 104 (3) ◽  
pp. 295-302 ◽  
Author(s):  
Mario VAZ ◽  
A.V. BHARATHI ◽  
S. SUCHARITA ◽  
D. NAZARETH
Keyword(s):  
Heart Rate ◽  
Heart Rate Variability ◽  
High Frequency ◽  
Baroreflex Sensitivity ◽  
Human Subjects ◽  
Normal Weight ◽  
Autonomic Nerve ◽  
Total Power ◽  
Healthy Human ◽  
Frequency Power

Alterations in autonomic nerve activity in subjects in a chronically undernourished state have been proposed, but have been inadequately documented. The present study evaluated heart rate and systolic blood pressure variability in the frequency domain in two underweight groups, one of which was undernourished and recruited from the lower socio-economic strata [underweight, undernourished (UW/UN); n = 15], while the other was from a high class of socio-economic background [underweight, well nourished (UW/WN); n = 17], as well as in normal-weight controls [normal weight, well nourished (NW/WN); n = 27]. Baroreflex sensitivity, which is a determinant of heart rate variability, was also assessed. The data indicate that total power (0–0.4Hz), low-frequency power (0.04–0.15Hz) and high-frequency power (0.15–0.4Hz) of RR interval variability were significantly lower in the UW/UN subjects (P<0.05) than in the NW/WN controls when expressed in absolute units, but not when the low- and high-frequency components were normalized for total power. Baroreflex sensitivity was similarly lower in the UW/UN group (P<0.05). Heart rate variability parameters in the UW/WN group were generally between those of the UW/UN and NW/WN groups, but were not statistically different from either. The mechanisms that contribute to the observed differences between undernourished and normal-weight groups, and the implications of these differences, remain to be elucidated.

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