scholarly journals Clinical Re-evaluation on Bioequivalence and Relative Bioavailability of Micronized Progesterone Hard Capsule (Yimaxin) and Micronized Progesterone Soft Capsule (Utrogestan) under Vaginal and Oral Administration Routes

2021 ◽  
Vol 37 (7) ◽  
Author(s):  
Hanbi Wang ◽  
Meizhi Liu ◽  
Rui Chen ◽  
Chenyan Deng
Keyword(s):  
Oral Administration ◽  
Relative Bioavailability ◽  
Endometrial Biopsy ◽  
Administration Route ◽  
Creative Commons ◽  
Administration Routes ◽  
Vaginal Administration ◽  
Open Access Article ◽  
Micronized Progesterone

Background and Objective: To clinically re-evaluate relative bioavailability and bioequivalence of micronized progesterone (hard capsule) Yimaxin and micronized progesterone (soft capsule) Utrogestan under vaginal and oral administration routes. Methods: From December 2017 to June 2018, a total of 16 postmenopausal healthy women were recruited and received a total of four rounds of drug treatment with cross-over design, respectively Yimaxin and Utrogestan under vaginal and oral administration routes. Changes in the subjects’ hormone levels after medication were monitored and an endometrial biopsy after a course of treatment was performed in our hospital. Result: The Geomeans of AUC0-t of Yimaxin and Utrogestan under vaginal administration route were 252.15 and 115.46, respectively, with a ratio of 2.19, and under oral administration route were 244.64 and 413.68, respectively, with a ratio of 0.59. The Geomeans of Cmax of Yimaxin and Utrogestan under vaginal administration route were 28.11 and 12.21, respectively, with a ratio of 2.30, and under oral administration route were 53.12 and 129.85, respectively, with a ratio of 0.41. Conclusion: Yimaxin was not bioequivalent to Utrogestan. Yimaxin had higher exposure to the drug in vivo at the same dose when administered vaginally, and Utrogestan had higher exposure to the drug in vivo at the same dose when administered orally. doi: https://doi.org/10.12669/pjms.37.7.3949 How to cite this:Wang H, Liu M, Chen R, Deng C. Clinical Re-evaluation on Bioequivalence and Relative Bioavailability of Micronized Progesterone Hard Capsule (Yimaxin) and Micronized Progesterone Soft Capsule (Utrogestan) under Vaginal and Oral Administration Routes. Pak J Med Sci. 2021;37(7):---------. doi: https://doi.org/10.12669/pjms.37.7.3949 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

scholarly journals Pharmacokinetic Comparison of Three Different Administration Routes for Topotecan Hydrochloride in Rats

2020 ◽  
Vol 13 (9) ◽  
pp. 231
Author(s):  
Seung-Hyun Jeong ◽  
Ji-Hun Jang ◽  
Yong-Bok Lee
Keyword(s):  
Oral Administration ◽  
Plasma Concentrations ◽  
Subcutaneous Administration ◽  
Pharmacokinetic Parameters ◽  
Pharmacokinetic Studies ◽  
Elimination Phase ◽  
Routes Of Administration ◽  
Administration Routes ◽  
Pharmacokinetic Profiles

Topotecan is actively used in clinic, with its primary use being in treatment of various types of cancer. The approved administration routes are oral and intravenous. The purpose of this study was to investigate and identify pharmacokinetic profiles of different administration routes. We conducted pharmacokinetic studies on three different routes of administration in rats. Five rats in each group received a single dose of 4 mg/kg of topotecan hydrochloride intravenously, orally, or subcutaneously, and the concentrations of lactone and total forms of the drug in plasma, urine, and feces were quantified. Various pharmacokinetic parameters were compared statistically. Plasma concentrations of both the lactone and total forms at elimination phase following subcutaneous administration, were two times higher than was seen with oral administration and 10 times higher than with intravenous administration. Subcutaneous administration of topotecan showed pharmacokinetic profiles similar to sustained release. In addition, subcutaneous administration showed bioavailability from 88.05% (for lactone form) to 99.75% (for total form), and these values were four–five times greater than those of oral administration. The results of this non-clinical study will not only provide greater understanding of the in vivo pharmacokinetics of topotecan, but also be useful for development of additional formulations and/or administration routes.

Delivery Efficacy Differences of Intravenous and Intraperitoneal Injection of Exosomes: Perspectives from Tracking Dye Labeled and MiRNA Encapsulated Exosomes

2020 ◽  
Vol 17 (3) ◽  
pp. 186-194 ◽  
Author(s):  
Xueying Zhou ◽  
Zhelong Li ◽  
Wenqi Sun ◽  
Guodong Yang ◽  
Changyang Xing ◽  
...  
Keyword(s):  
Intraperitoneal Injection ◽  
Drug Delivery Vehicles ◽  
C Elegans ◽  
Administration Routes ◽  
In Vivo Distribution ◽  
Obesity Therapy ◽  
Delivery Vehicles ◽  
Visceral Adipose ◽  
Mirna Abundance

Background: Exosomes are cell-derived nanovesicles that play vital roles in intercellular communication. Recently, exosomes are recognized as promising drug delivery vehicles. Up till now, how the in vivo distribution of exosomes is affected by different administration routes has not been fully understood. Methods: In the present study, in vivo distribution of exosomes following intravenous and intraperitoneal injection approaches was systemically analyzed by tracking the fluorescence-labeled exosomes and qPCR analysis of C. elegans specific miRNA abundance delivered by exosomes in different organs. Results: The results showed that exosomes administered through tail vein were mostly taken up by the liver, spleen and lungs while exosomes injected intraperitoneally were more dispersedly distributed. Besides the liver, spleen, and lungs, intraperitoneal injection effectively delivered exosomes into the visceral adipose tissue, making it a promising strategy for obesity therapy. Moreover, the results from fluorescence tracking and qPCR were slightly different, which could be explained by systemic errors. Conclusion: Together, our study reveals that different administration routes cause a significant differential in vivo distribution of exosomes, suggesting that optimization of the delivery route is prerequisite to obtain rational delivery efficiency in detailed organs.

A Comparative Pharmacokinetic Profile of Trahydropalmatine After Oral Administration of its Monomer, Rhizoma Corydalis Alkaloid Extracts and Tong-Bi-Si-Wei-Fang to Rats

2019 ◽  
Vol 15 (4) ◽  
pp. 338-345
Author(s):  
Lijun Ni ◽  
Lu Ding ◽  
Liguo Zhang ◽  
Shaorong Luan
Keyword(s):  
Oral Administration ◽  
Panax Notoginseng ◽  
Pharmacokinetic Profile ◽  
Apparent Volume ◽  
Bone Diseases ◽  
Glycyrrhiza Uralensis ◽  
Pharmacokinetic Property ◽  
Time Curve ◽  
Concentration Time

Background: Tong-Bi-Si-Wei-Fang (TBSWF) is a candidate formula of Traditional Chinese Medicine (TCM) for treating rheumatoid bone diseases, which is composed of rhizoma corydalis alkaloids, saponins of glycyrrhiza uralensis and panax notoginseng, flavonoids of rhizoma drynariae and glycyrrhiza uralensis. </P><P> Objective: Trahydropalmatine (THP), the main active ingredient of rhizoma corydalis alkaloids, was selected to study in vivo pharmacokinetics and druggability of TBSWF. Methods: The plasma concentration-time (C-T) profiles of THP and the pharmacokinetic property parameters after oral administration of THP monomer, extract of corydalis alkaloids (ECA) and TBSWF to rats, respectively were compared by a fully-validated HPLC method. Results: Compared to the THP monomer, the THP in TBSWF is absorbed faster, resides in the plasma longer and has a similar apparent volume of distribution Vz/F (10~20 L/kg). Compared to THP monomer and THP in TBSWF, the area under the concentration-time curve AUC 0-t of THP in ECA decreases two-third; Vz/F of THP in ECA (85.02 L/kg) is significantly higher than that of THP in TBSWF(p <0.05). Unlike THP monomer and THP in ECA, double peaks are observed in the C-T profile of THP after oral administration of TBSWF. THP in TBSWF exhibits slow release to a certain degree. Conclusion: The interactions among the ingredients of TBSWF promote the adsorption and prolong the residence time of THP in vivo, and provide an explanation for the advantages of TBSWF from the point of pharmacokinetics.

Oral Administration of Starting Materials for In Vivo Synthesis of Antibacterial Gold Nanoparticles for Curing Remote Infections

Nano Letters ◽  
2021 ◽  
Vol 21 (2) ◽  
pp. 1124-1131
Author(s):  
Le Wang ◽  
Junchuan Yang ◽  
Sixiang Li ◽  
Qizhen Li ◽  
Shaoqin Liu ◽  
...  
Keyword(s):  
Gold Nanoparticles ◽  
Oral Administration ◽  
In Vivo Synthesis

scholarly journals In-vitro and in-vivo metabolism of different aspirin formulations studied by a validated liquid chromatography tandem mass spectrometry method

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Michele Dei Cas ◽  
Jessica Rizzo ◽  
Mariangela Scavone ◽  
Eti Femia ◽  
Gian Marco Podda ◽  
...  
Keyword(s):  
Oral Administration ◽  
Whole Blood ◽  
Serum Levels ◽  
Reversed Phase ◽  
Weekly Treatment ◽  
Low Dose Aspirin ◽  
Liquid Chromatography Tandem Mass ◽  
Enteric Coated

AbstractLow-dose aspirin (ASA) is used to prevent cardiovascular events. The most commonly used formulation is enteric-coated ASA (EC-ASA) that may be absorbed more slowly and less efficiently in some patients. To uncover these “non-responders” patients, the availability of proper analytical methods is pivotal in order to study the pharmacodynamics, the pharmacokinetics and the metabolic fate of ASA. We validated a high-throughput, isocratic reversed-phase, negative MRM, LC–MS/MS method useful for measuring circulating ASA and salicylic acid (SA) in blood and plasma. ASA-d4 and SA-d4 were used as internal standards. The method was applied to evaluate: (a) the "in vitro" ASA degradation by esterases in whole blood and plasma, as a function of time and concentration; (b) the "in vivo" kinetics of ASA and SA after 7 days of oral administration of EC-ASA or plain-ASA (100 mg) in healthy volunteers (three men and three women, 37–63 years). Parameters of esterases activity were Vmax 6.5 ± 1.9 and Km 147.5 ± 64.4 in plasma, and Vmax 108.1 ± 20.8 and Km 803.2 ± 170.7 in whole blood. After oral administration of the two formulations, tmax varied between 3 and 6 h for EC-ASA and between 0.5 and 1.0 h for plain-ASA. Higher between-subjects variability was seen after EC-ASA, and one subject had a delayed absorption over eight hours. Plasma AUC was 725.5 (89.8–1222) for EC-ASA, and 823.1(624–1196) ng h/mL (median, 25–75% CI) for plain ASA. After the weekly treatment, serum levels of TxB2 were very low (< 10 ng/mL at 24 h from the drug intake) in all the studied subjects, regardless of the formulation or the tmax. This method proved to be suitable for studies on aspirin responsiveness.

scholarly journals Sulpiride Serves, a Substrate for the Gut Microbiome

Dose-Response ◽  
2021 ◽  
Vol 19 (1) ◽  
pp. 155932582098794
Author(s):  
Imran Mukhtar ◽  
Haseeb Anwar ◽  
Osman Asghar Mirza ◽  
Qasim Ali ◽  
Muhammad Umar Ijaz ◽  
...  
Keyword(s):  
Oral Administration ◽  
Gut Microbiome ◽  
Drug Target ◽  
Membrane Transporters ◽  
Intestinal Microbiome ◽  
Albino Rats ◽  
Body Organ ◽  
Total Absorbance ◽  
Research World

In the contemporary research world, the intestinal microbiome is now envisioned as a new body organ. Recently, the gut microbiome represents a new drug target in the gut, since various orthologues of intestinal drug transporters are also found present in the microbiome that lines the small intestine of the host. Owing to this, absorbance of sulpiride by the gut microbiome in an in vivo albino rats model was assessed after the oral administration with a single dose of 20mg/kg b.w. The rats were subsequently sacrificed at 2, 3, 4, 5 and 6 hours post oral administration to collect the gut microbial mass pellet. The drug absorbance by the gut microbiome was determined by pursuing the microbial lysate through RP-HPLC-UV. Total absorbance of sulpiride by the whole gut microbiome and drug absorbance per milligram of microbial pellet were found significantly higher at 4 hours post-administration as compared to all other groups. These results affirm the hypothesis that the structural homology between membrane transporters of the gut microbiome and intestinal epithelium of the host might play an important role in drug absorbance by gut microbes in an in vivo condition.

scholarly journals Administration route governs the therapeutic efficacy, biodistribution and macrophage targeting of anti-inflammatory nanoparticles in the lung

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Lu Wang ◽  
Yafei Rao ◽  
Xiali Liu ◽  
Liya Sun ◽  
Jiameng Gong ◽  
...  
Keyword(s):  
Therapeutic Efficacy ◽  
Lung Inflammation ◽  
Respiratory Diseases ◽  
Inflammatory Responses ◽  
The Other ◽  
Target Cells ◽  
Administration Route ◽  
Toll Like Receptor ◽  
Administration Routes ◽  
Anti Inflammatory

Abstract Background Uncontrolled inflammation is a central problem for many respiratory diseases. The development of potent, targeted anti-inflammatory therapies to reduce lung inflammation and re-establish the homeostasis in the respiratory tract is still a challenge. Previously, we developed a unique anti-inflammatory nanodrug, P12 (made of hexapeptides and gold nanoparticles), which can attenuate Toll-like receptor-mediated inflammatory responses in macrophages. However, the effect of the administration route on its therapeutic efficacy and tissue distribution remained to be defined. Results In this study, we systematically compared the effects of three different administration routes [the intratracheal (i.t.), intravenous (i.v.) and intraperitoneal (i.p.)] on the therapeutic activity, biodistribution and pulmonary cell targeting features of P12. Using the LPS-induced ALI mouse model, we found that the local administration route via i.t. instillation was superior in reducing lung inflammation than the other two routes even treated with a lower concentration of P12. Further studies on nanoparticle biodistribution showed that the i.t. administration led to more accumulation of P12 in the lungs but less in the liver and other organs; however, the i.v. and i.p. administration resulted in more nanoparticle accumulation in the liver and lymph nodes, respectively, but less in the lungs. Such a lung favorable distribution was also determined by the unique surface chemistry of P12. Furthermore, the inflammatory condition in the lung could decrease the accumulation of nanoparticles in the lung and liver, while increasing their distribution in the spleen and heart. Interestingly, the i.t. administration route helped the nanoparticles specifically target the lung macrophages, whereas the other two administration routes did not. Conclusion The i.t. administration is better for treating ALI using nanodevices as it enhances the bioavailability and efficacy of the nanodrugs in the target cells of the lung and reduces the potential systematic side effects.

scholarly journals Biodistribution of Mesenchymal Stromal Cells after Administration in Animal Models and Humans: A Systematic Review

2021 ◽  
Vol 10 (13) ◽  
pp. 2925
Author(s):  
Manuel Sanchez-Diaz ◽  
Maria I. Quiñones-Vico ◽  
Raquel Sanabria de la Torre ◽  
Trinidad Montero-Vílchez ◽  
Alvaro Sierra-Sánchez ◽  
...  
Keyword(s):  
Animal Models ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Cellular Therapy ◽  
The Body ◽  
Intralesional Injection ◽  
Intraarterial Infusion ◽  
Routes Of Administration ◽  
Administration Routes

Mesenchymal Stromal Cells (MSCs) are of great interest in cellular therapy. Different routes of administration of MSCs have been described both in pre-clinical and clinical reports. Knowledge about the fate of the administered cells is critical for developing MSC-based therapies. The aim of this review is to describe how MSCs are distributed after injection, using different administration routes in animal models and humans. A literature search was performed in order to consider how MSCs distribute after intravenous, intraarterial, intramuscular, intraarticular and intralesional injection into both animal models and humans. Studies addressing the biodistribution of MSCs in “in vivo” animal models and humans were included. After the search, 109 articles were included in the review. Intravenous administration of MSCs is widely used; it leads to an initial accumulation of cells in the lungs with later redistribution to the liver, spleen and kidneys. Intraarterial infusion bypasses the lungs, so MSCs distribute widely throughout the rest of the body. Intramuscular, intraarticular and intradermal administration lack systemic biodistribution. Injection into various specific organs is also described. Biodistribution of MSCs in animal models and humans appears to be similar and depends on the route of administration. More studies with standardized protocols of MSC administration could be useful in order to make results homogeneous and more comparable.

scholarly journals Benznidazole Extended-Release Tablets for Improved Treatment of Chagas Disease: Preclinical Pharmacokinetic Study

2016 ◽  
Vol 60 (4) ◽  
pp. 2492-2498 ◽  
Author(s):  
Marcelo Gomes Davanço ◽  
Michel Leandro Campos ◽  
Talita Atanazio Rosa ◽  
Elias Carvalho Padilha ◽  
Alejandro Henao Alzate ◽  
...  
Keyword(s):  
Chagas Disease ◽  
Extended Release ◽  
Hydroxypropyl Methylcellulose ◽  
Immediate Release ◽  
Relative Bioavailability ◽  
Pharmacokinetic Parameters ◽  
Therapeutic Success ◽  
Preclinical Pharmacokinetics ◽  
Bioavailability Study

ABSTRACTBenznidazole (BNZ) is the first-line drug for the treatment of Chagas disease. The drug is available in the form of immediate-release tablets for 100-mg (adult) and 12.5-mg (pediatric) doses. The drug is administered two or three times daily for 60 days. The high frequency of daily administrations and the long period of treatment are factors that significantly contribute to the abandonment of therapy, affecting therapeutic success. Accordingly, this study aimed to evaluate the preclinical pharmacokinetics of BNZ administered as extended-release tablets (200-mg dose) formulated with different types of polymers (hydroxypropyl methylcellulose K4M and K100M), compared to the tablets currently available. The studies were conducted with rabbits, and BNZ quantification was performed in plasma and urine by ultraperformance liquid chromatography methods previously validated. The bioavailability of BNZ was adequate in the administration of extended-release tablets; however, with the administration of the pediatric tablet, the bioavailability was lower than with other tablets, which showed that the clinical use of this formulation should be monitored. The pharmacokinetic parameters demonstrated that the extended-release tablets prolonged drug release from the pharmaceutical matrix and provided an increase in the maintenance of the drug concentrationin vivo, which would allow the frequency of administration to be reduced. Thus, a relative bioavailability study in humans will be planned for implementation of a new product for the treatment of Chagas disease.

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