scholarly journals EXPERIMENTAL PHARMACOKINETIC STUDY OF ZINC WHEN ZINC HYDROXIDE NANOFORM IS ADMINISTERED ENTERALY AND INTRAVASCULARY

2017 ◽  
Vol 25 (2) ◽  
pp. 193-201
Author(s):  
S. L. Larin ◽  
A. R. Zvyagintseva ◽  
A. A. Khabarov ◽  
E. V. Budko ◽  
E. B. Artushkova
Keyword(s):  
Sol Gel ◽  
Absorption Spectrometry ◽  
Absolute Bioavailability ◽  
Pharmacokinetic Parameters ◽  
Zinc Hydroxide ◽  
In Vivo Experiments ◽  
Experimental Pharmacokinetic ◽  
Enteral Administration ◽  
Wet Ashing

In vivo experiments on rabbits studied pharmacokinetic properties of Zn2+ under administration of zinc hydroxide nanoparticles (2-3 nm) that were obtained by sol-gel me-thod. Soluble zinc sulfate was selected as a comparison compound. Measurement of plasma Zn2+ levels was carried out by atomic absorption spectrometry with preliminary sample preparation method by wet ashing. Pharmacokinetic parameters were calculated after sin-gle enteral administration (doses 10, 50 and 100 mg/kg) and single intravenous injection (doses 10, 50 and 100 mg/kg). Absolute bioavailability for nanoparticles was found to have high values 33,013,55%, 45,153,68% and 43,182,71% for 10, 50 and 100 mg/kg enteral administration respectively.

Pharmacokinetics of ciclopirox prodrug, a novel agent for the treatment of bladder cancer, in animals and humans.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e14705-e14705 ◽  
Author(s):  
Scott James Weir ◽  
Robyn Wood ◽  
Michael Jay Baltezor ◽  
Greg Reed ◽  
Amanda E Brinker ◽  
...  
Keyword(s):  
Phase 1 ◽  
Systemic Exposure ◽  
Absolute Bioavailability ◽  
Pharmacokinetic Parameters ◽  
Time Data ◽  
Elimination Half ◽  
Urine Drug ◽  
Ic50 Values

e14705 Background: Ciclopirox Prodrug (CPX-POM) is a novel anticancer agent currently being evaluated in patients with advanced solid tumors participating in a First-in-Human, Phase 1 safety, dose tolerance, pharmacokinetics (PK) and pharmacodynamics trial at four US sites. In vitro and in vivo preclinical proof of principle was established in high grade human urothelial cancer cell lines as well as a mouse model of bladder cancer.Methods: A series of in vivo PK studies were conducted in mice, rats and dogs to characterize the absolute bioavailability of CPX following intravenous (IV), subcutaneous (SC) and oral administration of CPX-POM. The single dose and steady-state plasma and urine pharmacokinetics of CPX-POM are also currently being characterized in patients participating in the ongoing Phase 1 trial. Plasma and urine concentrations of the prodrug and metabolites were determined by LC-MS/MS validated in each specie and matrix. Non-parametric pharmacokinetic parameters were generated from resultant plasma and urine drug and metabolite concentration-time data. Results: CPX-POM is rapidly and completely metabolized to CPX in blood via circulating phosphatases in animals and humans. CPX is completely bioavailable following IV CPX-POM administration in mice, rats and dogs. CPX and its major inactive glucuronide metabolite (CPX-G) are extensively eliminated in urine in all animal species. SC administration of CPX-POM demonstrated excellent bioavailability in rats and dogs. Following IV administration of 30-900 mg/m2CPX-POM to patients, the apparent elimination half-life of CPX ranged from 2 to 8 hours, CPX systemic exposure was dose-proportional and time-independent in cancer patients, and a major portion of the dose was eliminated as CPX-G. Conclusions: IV CPX-POM achieves plasma and urine CPX exposures that exceed in vitro IC50 values several-fold at well tolerated doses in animals and humans. CPX pharmacokinetics observed in animals were predictive of human systemic clearance based on allometric scaling. Clinical trial information: NCT03348514.

scholarly journals Celecoxib confinement within mesoporous silicon for enhanced oral bioavailability

2014 ◽  
Vol 1 (1) ◽  
Author(s):  
Feng Wang ◽  
Timothy J. Barnes ◽  
Clive A. Prestidge
Keyword(s):  
Physicochemical Characteristics ◽  
In Vitro Dissolution ◽  
Absolute Bioavailability ◽  
Dissolution Behavior ◽  
Pharmacokinetic Parameters ◽  
Mesoporous Silicon ◽  
Silicon Matrix ◽  
Oxidized Porous Silicon

AbstractWe investigate the physicochemical characteristics of celecoxib (CEL) entrapped within particles of an oxidized porous silicon matrix (pSiox); determine the oral dose response of CEL compared to pure drug and innovator formulation; develop in vivo-in vitro correlation (IVIVC). CEL was loaded into a pSiox matrix by solvent partitioning, with the physical state of the CEL characterized by FTIR, DSC, TGA and XRD, and correlated with in vitro dissolution behavior. Single dose pharmacokinetic parameters of orally dosed CEL were determined in fasted rats for aqueous suspensions of pure CEL, Celebrexr and CEL-pSiox microparticles. Physicochemical testing of CEL-pSiox formulation confirmed the entrapment of CEL within porous nanostructure in an amorphous or non-crystalline form. CEL-pSiox demonstrated superior pharmacokinetics compared with CEL particles or Celebrexr, i.e. increased absolute bioavailability (96.2% vs. 65.2% vs. 88.1%), increased C

Bioavailability and Speciation of Mineral Micronutrients: The Enzymolysis Approach

1997 ◽  
Vol 80 (4) ◽  
pp. 920-927 ◽  
Author(s):  
Pierre Hocquellet ◽  
Marie-Dominique L'Hotellier
Keyword(s):  
Gastrointestinal Tract ◽  
Absorption Spectrometry ◽  
Insoluble Residue ◽  
In Vivo Experiments ◽  
Treatment Data ◽  
Dietary Components ◽  
Vitro Model ◽  
Good Agreement

Abstract Speciation analyses are essential to investigate the effects of dietary components on bioavailability of mineral micronutrients. Enzymolysis was used. An in vitro model simulating enzymatic activity in the gastrointestinal tract of monogastric species was developed and used to assess availability of Fe, Cu, Mn, and Zn in some foodstuffs. The solubility of each element in samples was measured by atomic absorption spectrometry after enzymatic treatment. Data are in good agreement with information obtained from earlier, more expensive nutritional surveys or in vivo experiments and, therefore, allow prediction of the tendency of a particular food to induce mineral deficiency. In addition, ligands responsible for inhibiting intestinal absorption were identified by determining the amount of metal released after treatment of the insoluble residue with an appropriate enzyme such as cellulase and phytase, used respectively to study fiber and phytate interactions. Enzymolysis may be useful for optimizing mineral supplementations though its nutritional significance is somewhat limited by the fact that it does not take into account the dynamic changes in the gastrointestinal tract. Enzymolysis is a prerequisite for further speciation studies of complex systems and in some instances is the only way for specifying physicochemical forms of elements.

scholarly journals The LC-MS/MS-Based Measurement of Isopimaric Acid in Rat Plasma and Application of Pharmacokinetics

2021 ◽  
Vol 2021 ◽  
pp. 1-9
Author(s):  
Doudou Huang ◽  
Jiaxi Cheng ◽  
Junqin Mao ◽  
Senlin Ma ◽  
Zenan Du ◽  
...  
Keyword(s):  
Internal Standard ◽  
Rat Plasma ◽  
Absolute Bioavailability ◽  
Pharmacokinetic Analysis ◽  
Pharmacokinetic Parameters ◽  
Isopimaric Acid ◽  
Clinical Utilization ◽  
Mechanistic Basis ◽  
Oral Doses

Isopimaric acid (IPA) exhibits a diverse array of pharmacological activities, having been shown to function as an antihypertensive, antitumor, antibacterial, and hypocholesterolemic agent. However, few studies of the pharmacokinetics of IPA have been performed to date, and such analyses are essential to explore the in vivo mechanisms governing the biological activity of this compound. As such, we herein designed a selective LC-MS approach capable of quantifying serum IPA levels in model rats using an Agilent HC-C18 column ( 250   mm × 4.6   mm , 5 μm) via isocratic elution with a mobile phase composed of methanol 0.5% formic acid (91 : 9, v/v) at a 1 mL/min flow rate. Ion monitoring at m/z 301.2 [M-H]- was used to quantify IPA levels in plasma samples from these rats, while internal standard (IS) levels were assessed at m/z 455.3 [M-H]-. After validation, this approach was employed to conduct a pharmacokinetic analysis of rats administered IPA via the oral (p.o. 50, 100, or 200 mg/kg) and intravenous (i.v. 5 mg/kg) routes. Analyses of noncompartmental pharmacokinetic parameters revealed that IPA underwent secondary absorption following oral administration to these animals, with the two tested oral doses (50 and 100 mg/kg) being associated with respective absolute bioavailability values of 11.9% and 17.5%. In summary, this study may provide a foundation for future efforts to explore the mechanistic basis for the pharmacological activity of IPA, offering insights to guide its subsequent clinical utilization.

scholarly journals Pharmacological Properties of a New Antimalarial Bisthiazolium Salt, T3, and a Corresponding Prodrug, TE3

2005 ◽  
Vol 49 (9) ◽  
pp. 3631-3639 ◽  
Author(s):  
Olivier Nicolas ◽  
Delphine Margout ◽  
Nicolas Taudon ◽  
Sharon Wein ◽  
Michèle Calas ◽  
...  
Keyword(s):  
Oral Administration ◽  
Antimalarial Activity ◽  
Plasma Concentrations ◽  
Intraperitoneal Administration ◽  
Absolute Bioavailability ◽  
Pharmacokinetic Parameters ◽  
Pharmacological Properties ◽  
Mean Values

ABSTRACT A new approach to malarial chemotherapy based on quaternary ammonium that targets membrane biogenesis during intraerythrocytic Plasmodium falciparum development has recently been developed. To increase the bioavailability, nonionic chemically modified prodrugs were synthesized. In this paper, the pharmacological properties of a bisthiazolium salt (T3) and its bioprecursor (TE3) were studied. Their antimalarial activities were determined in vitro against the growth of P. falciparum and in vivo against the growth of P. vinckei in mice. Pharmacokinetic evaluations were performed after T3 (1.3 and 3 mg/kg of body weight administered intravenously; 6.4 mg/kg administered intraperitoneally) and TE3 (1.5 and 3 mg/kg administered intravenously; 12 mg/kg administered orally) administrations to rats. After intraperitoneal administration, very low doses offer protection in a murine model of malaria (50% efficient dose [ED50] of 0.2 to 0.25 mg/kg). After oral administration, the ED50 values were 13 and 5 mg/kg for T3 and TE3, respectively. Both compounds exerted antimalarial activity in the low nanomolar range. After TE3 administration, rapid prodrug-drug conversion occurred; the mean values of the pharmacokinetic parameters for T3 were as follows: total clearance, 1 liter/h/kg; steady-state volume of distribution, 14.8 liters/kg; and elimination half-life, 12 h. After intravenous administration, T3 plasma concentrations increased in proportion to the dose. The absolute bioavailability was 72% after intraperitoneal administration (T3); it was 15% after oral administration (TE3). T3 plasma concentrations (8 nM) 24 h following oral administration of TE3 were higher than the 50% inhibitory concentrations for the most chloroquine-resistant strains of P. falciparum (6.3 nM).

A Multicenter Study of Recombinant Factor VIII (RecombinateTM) in Previously Treated Patients with Hemophilia A

1997 ◽  
Vol 77 (04) ◽  
pp. 660-667 ◽  
Author(s):  
G C White ◽  
S Courter ◽  
G L Bray ◽  
M Lee ◽  
E D Gomperts ◽  
...  
Keyword(s):  
Hemophilia A ◽  
Recombinant Dna ◽  
Home Treatment ◽  
Pharmacokinetic Parameters ◽  
Pharmacokinetic Studies ◽  
Open Label ◽  
Treat Ment ◽  
Previously Treated Patients ◽  
Bleeding Episodes

SummaryA prospective, open-label multicenter investigation has been conducted to compare pharmacokinetic parameters of recombinant DNA-derived FVIII (rFVIII) and plasma-derived FVIII concentrate (pdFVIII) and to assess safety and efficacy of long-term home-treat- ment with rFVIII for subjects with hemophilia A. Following comparative in vivo pharmacokinetic studies, 69 patients with severe (n = 67) or moderate (n = 2) hemophilia A commenced a program of home treatment using rFVIII exclusively for prophylaxis and treatment of all bleeding episodes for a period of 1.0 to 5.7 years (median 3.7 years). The mean in vivo half-lives of rFVIII and pdFVIII were both 14.7 h. In vivo incremental recoveries at baseline were 2.40%/IU/kg and 2.47%/IU/kg, respectively (p = 0.59). The response to home treatment with rFVIII was categorized as good or excellent in 3,195 (91.2%) of 3,481 evaluated bleeding episodes. Thirteen patients received rFVIII for prophylaxis for twenty-four surgical procedures. In all cases, hemostasis was excellent. Adverse reactions were observed in only 13 of 13,591 (0.096%) infusions of rFVIII; none was serious. No patient developed an inhibitor to r FVIII.

Tantalum Oxide Nanoparticles as Versatile Contrast Agents for X-ray Computed Tomography

2020 ◽  
Author(s):  
Shatadru Chakravarty ◽  
Jeremy Hix ◽  
Kaitlyn Wieweora ◽  
Maximilian Volk ◽  
Elizabeth Kenyon ◽  
...  
Keyword(s):  
Computed Tomography ◽  
Contrast Agents ◽  
Mesoporous Silica Nanoparticles ◽  
Sol Gel ◽  
Tantalum Oxide ◽  
High Signal ◽  
Drug Delivery Vehicles ◽  
X Ray Computed

Here we describe the synthesis, characterization and in vitro and in vivo performance of a series of tantalum oxide (TaOx) based nanoparticles (NPs) for computed tomography (CT). Five distinct versions of 9-12 nm diameter silane coated TaOx nanocrystals (NCs) were fabricated by a sol-gel method with varying degrees of hydrophilicity and with or without fluorescence, with the highest reported Ta content to date (78%). Highly hydrophilic NCs were left bare and were evaluated in vivo in mice for micro-CT of full body vasculature, where following intravenous injection, TaOx NCs demonstrate high CT contrast, circulation in blood for ~ 3 h, and eventual accumulation in RES organs; and following injection locally in the mammary gland, where the full ductal tree structure can be clearly delineated. Partially hydrophilic NCs were encapsulated within mesoporous silica nanoparticles (MSNPs; TaOx@MSNPs) and hydrophobic NCs were encapsulated within poly(lactic-co-glycolic acid) (PLGA; TaOx@PLGA) NPs, serving as potential CT-imagable drug delivery vehicles. Bolus intramuscular injections of TaOx@PLGA NPs and TaOx@MSNPs to mimic the accumulation of NPs at a tumor site produce high signal enhancement in mice. In vitro studies on bare NCs and formuated NPs demonstrate high cytocompatibility and low dissolution of TaOx. This work solidifies that TaOx-based NPs are versatile contrast agents for CT.

Stem Cell Cure for Kidney Injury: Therapy to Solve Most Complex Issues in Renal System

2020 ◽  
Author(s):  
Prithiv K R Kumar
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Kidney Injury ◽  
Cell Types ◽  
Tissue Remodelling ◽  
Major Health Problem ◽  
In Vivo Experiments ◽  
Renal Regeneration ◽  
Induced Pluripotent

Renal failure is a major health problem. The mortality rate remain high despite of several therapies. The most complex of the renal issues are solved through stem cells. In this review, different mechanism for cure of chronic kidney injury along with cell engraftment incorporated into renal structures will be analysed. Paracrine activities of embryonic or induced Pluripotent stem cells are explored on the basis of stem cell-induced kidney regeneration. Several experiments have been conducted to advance stem cells to ensure the restoration of renal functions. More vigour and organised protocols for delivering stem cells is a possibility for advancement in treatment of renal disease. Also there is a need for pressing therapies to replicate the tissue remodelling and cellular repair processes suitable for renal organs. Stem cells are the undifferentiated cells that have the ability to multiply into several cell types. In vivo experiments on animal’s stem cells have shown significant improvements in the renal regeneration and functions of organs. Nevertheless more studies show several improvements in the kidney repair due to stem cell regeneration.

Cationic Diclofenac Lipid Nanoemulsion for Improved Oral Bioavailability: Preparation, Characterization and In Vivo Evaluation

2015 ◽  
Vol 8 (2) ◽  
pp. 2874-2880
Author(s):  
Kishan Veerabrahma ◽  
Swapna Madishetty ◽  
Muzammil Afzal Syed ◽  
Prabhakar Kandadi
Keyword(s):  
Oral Bioavailability ◽  
Physical Stability ◽  
Cationic Lipid ◽  
Entrapment Efficiency ◽  
In Vivo Studies ◽  
Pharmacokinetic Parameters ◽  
In Vivo Evaluation ◽  
Drug Content ◽  
Lipid Nanoemulsion

Cationic nanoemulsions were reported to have increased bioavailability. The aim of present study was to prepare a cationic lipid nanoemulsion of diclofenac acid (LNEs) for improved oral bioavailability to treat arthritic conditions. The LNEs of diclofenac acid were prepared by using soya bean oil, egg lecithin, cholesterol and stearylamine. Stearylamine was used as positive charge inducer. The LNEs were processed by homogenization and ultrasonication. The formulation composition was selected based on earlier reports. The LNEs were characterized for size and zeta potential. The physical stability of LNEs was studied using autoclaving, centrifugal, desorption (dilution effect) stresses and on storage. The total drug content and entrapment efficiency were determined using HPLC. During in vivo studies in Wistar rats, the pharmacokinetic parameters of LNEs were compared with a prepared diclofenac suspension in sodium CMC mucilage. The selected formulations, F1, F2 and F3, were relatively stable during centrifugal stress, dilution stress and on storage. The drug content was found to be 2.38 ± 1.70 mg/ml for F1, 2.30 ± 0.82 mg/ml for F2, and 2.45 ± 0.66 mg/ml for F3. The entrapment efficiencies were 97.83 ± 0.53%, 97.87 ± 1.22% and 98.25 ± 0.21% for F1, F2 and F3 respectively. The cumulative percentage drug release from F1, F2 and F3 showed more release in pH 6.8 phosphate buffer than in pH 1.2 HCl. During oral bioavailability studies, the LNEs showed higher serum concentrations than a suspension. The relative bioavailability of the LNE formulations F1, F2 and F3 were found to be 2.35, 2.94 and 6.28 times that of F4 suspension and were statistically significant. Of all, the cationic lipid nanoemulsion (F3) was superior in improving bioavailability, when compared with plain emulsion (F1) and cholesterol containing LNE (F2). The study helps in designing the cationic oral nanoemulsions to improve the oral bioavailability of diclofenac.

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