scholarly journals Pre-Clinical Pharmacokinetic Characterization, Tissue Distribution, and Excretion Studies of Novel Edaravone Oral Prodrug, TEJ-1704

Pharmaceutics ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 1406
Author(s):  
Dong Wook Kang ◽  
Ju Hee Kim ◽  
Kyung Min Kim ◽  
Seok-jin Cho ◽  
Hee-Woon Jang ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Tissue Distribution ◽  
Animal Experiments ◽  
Oral Formulation ◽  
Free Radical Scavenger ◽  
Radical Scavenger ◽  
Beagle Dogs ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Oral Prodrug

Edaravone (3-methyl-1-phenyl-2-pyrazolin-5-one) is a free radical scavenger approved for the treatment of amyotrophic lateral sclerosis, a fatal neuromuscular disease. Edaravone is administered as an intravenous infusion over 60 min for several treatment cycles. To ease the burden of patients and caregivers, the oral formulation of edaravone has been developed. The purpose of this study was to evaluate pharmacokinetics and tissue distribution of TEJ-1704, an edaravone oral prodrug, in male Sprague Dawley rats and beagle dogs. Animal experiments were conducted using Sprague Dawley rats and beagle dogs to evaluate pharmacokinetics, tissue distribution, and excretion of TEJ-1704. Blood, tissues, cerebrospinal fluid, urine, and feces samples were collected at designated sampling time after intravenous (IV) or oral (PO) administration of edaravone or TEJ-1704. A modified bioanalysis method was developed to quantify edaravone in samples including plasma, tissues, cerebrospinal fluid, urine, and feces. The bioanalysis method was validated and successfully applied to pharmacokinetics, tissue distribution, and excretion studies of the novel edaravone prodrug. Although plasma Cmax of TEJ-1704 was low, groups administered with TEJ-1704 had high AUCinf, suggesting continuous metabolism of TEJ-1704 into edaravone. Groups treated with TEJ-1704 also showed lower CSF distribution than the control groups. After the administration of TEJ-1704, the majority of edaravone was distributed to the heart, lung, and kidney. It was excreted equally via urine and feces. The pharmacokinetics, tissue distribution, and excretion of TEJ-1704, a novel edaravone oral prodrug, were successfully characterized. Additional studies are needed to fully understand the difference between TEJ-1704 and edaravone and determine the potency of TEJ-1704.

scholarly journals Phenyl N -tert-butylnitrone, a Free Radical Scavenger, Reduces Mechanical Allodynia in Chemotherapy-induced Neuropathic Pain in Rats

2010 ◽  
Vol 112 (2) ◽  
pp. 432-439 ◽  
Author(s):  
Hee Kee Kim ◽  
Yan Ping Zhang ◽  
Young Seob Gwak ◽  
Salahadin Abdi
Keyword(s):  
Neuropathic Pain ◽  
Free Radical ◽  
Mechanical Allodynia ◽  
Intraperitoneal Administration ◽  
Free Radical Scavenger ◽  
Radical Scavenger ◽  
Dependent Manner ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Dose Dependent

Background Paclitaxel is a widely used chemotherapeutic drug for breast and ovarian cancer. Unfortunately, it induces neuropathic pain, which is a dose-limiting side effect. Free radicals have been implicated in many neurodegenerative diseases. The current study tests the hypothesis that a free radical scavenger plays an important role in reducing chemotherapy-induced neuropathic pain. Methods Neuropathic pain was induced by intraperitoneal injection of paclitaxel (2 mg/kg) on four alternate days (days 0, 2, 4, and 6) in male Sprague-Dawley rats. Phenyl N-tert-butylnitrone (PBN), a free radical scavenger, was administered intraperitoneally as a single dose or multiple doses before or after injury. Mechanical allodynia was measured by using von Frey filaments. Results The administration of paclitaxel induced mechanical allodynia, which began to manifest on days 7-10, peaked within 2 weeks, and plateaued for at least 2 months after the first paclitaxel injection. A single injection or multiple intraperitoneal injections of PBN ameliorated paclitaxel-induced pain behaviors in a dose-dependent manner. Further, multiple administrations of PBN starting on day 7 through day 15 after the first injection of paclitaxel completely prevented the development of mechanical allodynia. However, an intraperitoneal administration of pbn for 8 days starting with the first paclitaxel injection did not prevent the development of pain behavior. Conclusions This study clearly shows that PBN alleviated mechanical allodynia induced by paclitaxel in rats. Furthermore, our data show that PBN given on days 7 through 15 after the first paclitaxel injection prevented the development of chemotherapy-induced neuropathic pain. This clearly has a clinical implication.

Soy Isoflavones Modify Liver Free Radical Scavenger Systems and Liver Parameters in Sprague–Dawley Rats

2004 ◽  
Vol 7 (4) ◽  
pp. 477-481 ◽  
Author(s):  
William Banz ◽  
Steve Hauck ◽  
Brian Gename ◽  
Todd Winters ◽  
Andrzej Bartke
Keyword(s):  
Free Radical ◽  
Free Radical Scavenger ◽  
Soy Isoflavones ◽  
Radical Scavenger ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Liver Parameters

Intraneuronal accumulations of lysosomes in the cerebellum of rats and dogs after dosing with MDL-832

1990 ◽  
Vol 48 (3) ◽  
pp. 830-831
Author(s):  
S.D. Barnard ◽  
S.D. Warner
Keyword(s):  
Brown Pigment ◽  
Beagle Dogs ◽  
Sprague Dawley ◽  
Gelatin Capsules ◽  
Pigment Granules ◽  
Sprague Dawley Rats ◽  
Hematoxylin And Eosin ◽  
Dose Levels

1, 2, 9, 10-tetramethoxyaporphine phosphate (MDL-832) was once considered a potential human antitussive. MDL-832 was administered orally in the diets of Sprague-Dawley rats at dose levels of 0, 5, 10, 20, 40, 80 and 160 mg/kg/day for 3 and 6 months and in gelatin capsules to Beagle dogs at 0, 5, 10, 15, 30 and 60 mg/kg/day for 3, 6 and 12 months. Histopathologic examinations of hematoxylin and eosin-stained cerebellar sections revealed intracytoplasmic brown pigment accumulations in large fusiform neurons (presumably the motor type) of the pons. The pigment granules were found to be PAS-positive, non-acid fast, iron-free, Sudan B-positive and fuchsinophilic. Intraneuronal pigment accumulations were seen in rats after 3 months of treatment at 80 mg but not at 40 mg and after 6 months at 20 mg but not at 10 mg. For dogs the effect was observed after 3 months at 60 mg but not at 30 mg and after 12 months at 10 mg but not at 5 mg.

scholarly journals Study on the pharmacokinetics, tissue distribution and excretion of laurolitsine from Litsea glutinosa in Sprague-Dawley rats

2021 ◽  
Vol 59 (1) ◽  
pp. 884-892
Author(s):  
Yin-Feng Tan ◽  
Rui-Qi Wang ◽  
Wen-Ting Wang ◽  
Ying Wu ◽  
Ning Ma ◽  
...  
Keyword(s):  
Tissue Distribution ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Litsea Glutinosa

Pharmacokinetics, tissue distribution and excretion of ACT001 in Sprague-Dawley rats and metabolism of ACT001

2019 ◽  
Vol 1104 ◽  
pp. 29-39 ◽  
Author(s):  
Xiao-Nan Xi ◽  
Ning Liu ◽  
Qian-qian Wang ◽  
Hai-Ting Wu ◽  
Hai-Bo He ◽  
...  
Keyword(s):  
Tissue Distribution ◽  
Sprague Dawley ◽  
Sprague Dawley Rats

Application of Cryopreservation Technique in the Preservation of Rat Limbs

2020 ◽  
Author(s):  
Yu Tian ◽  
Nan Li ◽  
Wei Wang ◽  
Na Li
Keyword(s):  
Animal Experiments ◽  
Storage Conditions ◽  
Sprague Dawley ◽  
Uw Solution ◽  
Tissue Morphology ◽  
University Of Wisconsin ◽  
Sprague Dawley Rats ◽  
Nerve Bundles ◽  
Healthy Adult Male ◽  
The University

Abstract Objective: This study aims to observe the physiological and pathological changes of severed fingers (limbs) under different storage conditions through animal experiments, and to screen out the best preservation conditions. Medthods: Sixty healthy adult male Sprague-Dawley rats were selected and evenly divided into 4 preservation groups, including conventional low-temperature dry (CLTD), the university of wisconsin (UW) solution, cryopreservation and cryopreservation + UW solution preservation group. After harvesting the limbs, were preservated for 72 h and 7 days, respectively. Then the limbs were thawed and replanted in situ. Sciatic nerves were collected for hematoxylin and eosin (HE) staining, and observed the changes in tissue morphology. Results: Replantation was successful in 11 out of 15 rats (73%) in cryopreservation + UW group, and the walking function of the 9 (82%) rats in cryopreservation + UW group were significantly better than that of the cryopreservation preservation group. In addition, the HE staining results shown that the CLTD group nerve bundles were morphologically damaged, and there were more acellular structures and tissue fragments; the UW group nerve bundles were less injured and the perineurium was more complete and orderly; The nerve bundles in the cryopreservation group and cryopreservation + UW group are tightly arranged and the tissue morphology is regular; Compared with the cryopreservation + UW group, the complete of the cryopreservation group is not well. Conclusions: The cryopreservation technology combined with UW solution is a new and effective method for the severed limbs preserving.

Regional effect of naltrexone in the nucleus of the solitary tract in blockade of NPY-induced feeding

2000 ◽  
Vol 278 (2) ◽  
pp. R499-R503 ◽  
Author(s):  
C. M. Kotz ◽  
M. J. Glass ◽  
A. S. Levine ◽  
C. J. Billington
Keyword(s):  
Cerebrospinal Fluid ◽  
Food Intake ◽  
Paraventricular Nucleus ◽  
Opioid Receptors ◽  
The Other ◽  
Solitary Tract ◽  
Sprague Dawley ◽  
Regional Effect ◽  
Sprague Dawley Rats ◽  
Artificial Cerebrospinal Fluid

Naltrexone (NLTX) in the nucleus of the solitary tract (NTS) decreases feeding induced by neuropeptide Y (NPY) in the paraventricular nucleus (PVN). We sought to determine the NTS region most sensitive to NLTX blockade of PVN NPY-induced feeding. Male Sprague-Dawley rats were fitted with two cannulas; one in the PVN and one in a hindbrain region: caudal, medial, or rostral NTS or 1 mm outside the NTS. Animals received NLTX (0, 1, 3, 10, and 30 μg in 0.3 μl) into the hindbrain region just prior to PVN NPY (0.5 μg, 0.3 μl) or artificial cerebrospinal fluid (0.3 μl). Food intake was measured at 2 h following injection. PVN NPY stimulated feeding, and NLTX in the medial NTS significantly decreased NPY-induced feeding at 2 h, whereas administration of NLTX in the other hindbrain regions did not significantly influence PVN NPY induced feeding. These data suggest that opioid receptors in the medial NTS are most responsive to feeding signals originating in the PVN after NPY stimulation.

Acylcarnitines: drug absorption-enhancing agents in the gastrointestinal tract

1986 ◽  
Vol 251 (3) ◽  
pp. G332-G340 ◽  
Author(s):  
J. A. Fix ◽  
K. Engle ◽  
P. A. Porter ◽  
P. S. Leppert ◽  
S. J. Selk ◽  
...  
Keyword(s):  
Gastrointestinal Tract ◽  
Drug Absorption ◽  
Structural Integrity ◽  
Somatostatin Analogue ◽  
Beagle Dogs ◽  
Sprague Dawley ◽  
Solid Dosage Forms ◽  
Intestinal Tissue ◽  
Solid Dosage ◽  
Sprague Dawley Rats

Acylcarnitines were tested as potential absorption-enhancing agents for drugs that are poorly absorbed from the gastrointestinal tract. Urethan-anesthetized Sprague-Dawley rats and conscious Beagle dogs were used. Palmitoyl-DL-carnitine was the most effective acylcarnitine tested, although significant increases in drug absorption were observed with acylcarnitines containing C12 through C18 fatty acid chains. Palmitoyl-DL-carnitine afforded significant increases in the absorption of cefoxitin, gentamicin, cytarabine, somatostatin analogue, and alpha-methyldopa. The response to palmitoyl-DL-carnitine was concentration dependent and reversible within 60-120 min. Histological examination of the intestinal tissue revealed no apparent change in mucosal structural integrity at doses of palmitoyl-DL-carnitine that resulted in increased drug absorption. The acylcarnitines were effective in increasing drug absorption from the small intestine and the rectal compartment of both rats and dogs. The data also demonstrated effectiveness with aqueous and solid dosage forms (Witepsol H-15 suppositories). The data suggest that acylcarnitines may be effective and safe absorption-enhancing agents for a variety of drugs.

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