THE PHARMACOLOGY AND METABOLISM OF TESTOSTERONE UNDECANOATE (TU), A NEW ORALLY ACTIVE ANDROGEN

1975 ◽  
Vol 79 (4) ◽  
pp. 789-800 ◽  
Author(s):  
A. Coert ◽  
J. Geelen ◽  
J. de Visser ◽  
J. van der Vies
Keyword(s):  
Portal Vein ◽  
Oral Administration ◽  
Lymphatic System ◽  
Intestinal Wall ◽  
Testosterone Undecanoate ◽  
Androgenic Activity ◽  
Orally Active ◽  
Harmful Effects

ABSTRACT Testosterone undecanoate (TU), either dissolved in arachis oil or as micro-crystal suspension, displays androgenic activity on oral administration to rats in the Hershberger test. The solution in arachis oil is more active than the crystal suspension. When [3H]TU is administered orally to rats, most of it is metabolized in the intestinal wall. The majority of the metabolites probably lose their undecanoate group and are absorbed via the portal vein. The non-metabolized [3H]TU and at least two metabolites are absorbed exclusively via the lymphatic system. One of these metabolites has been identified as 5α-dihydrotestosterone undecanoate (5α-DHTU). TU has no harmful effects on the liver of the rabbits on oral administration.

COMPARISON OF THE METABOLISM OF TESTOSTERONE UNDECANOATE AND TESTOSTERONE IN THE GASTROINTESTINAL WALL OF THE RAT IN VITRO AND IN VIVO

1977 ◽  
Vol 86 (1) ◽  
pp. 216-224 ◽  
Author(s):  
J. Geelen ◽  
A. Coert ◽  
R. Meijer ◽  
J. van der Vies
Keyword(s):  
Small Intestine ◽  
Gastrointestinal Tract ◽  
Portal Vein ◽  
Oral Administration ◽  
Small Extent ◽  
Great Similarity ◽  
Testosterone Undecanoate ◽  
Different Parts

ABSTRACT The metabolism of testosterone undecanoate (TU) and testosterone (T) is studied in the gastrointestinal wall of the rat in vitro. A comparison is made with the in vivo metabolism of these compounds in the rat. The major metabolite first appearing during incubation of TU with the small intestine is T. Incubation of TU or T with the small intestine reveals a great similarity between the metabolite patterns obtained. This is also the case with the patterns derived from portal vein plasma upon oral administration of TU and T. Incubation of different parts of the gastrointestinal tract with TU or T shows that the greatest metabolic activity is located in the wall of the small intestine. Unlike T, TU is metabolized only to a small extent in the wall of the stomach and the large intestine.

TESTOSTERONE UNDECANOATE: A NEW ORALLY ACTIVE ANDROGEN

1975 ◽  
Vol 80 (1) ◽  
pp. 179-187 ◽  
Author(s):  
C. Hirschhäuser ◽  
C. R. N. Hopkinson ◽  
G. Sturm ◽  
A. Coert
Keyword(s):  
Gas Chromatography ◽  
Oral Administration ◽  
Replacement Therapy ◽  
Elevated Plasma ◽  
Testosterone Undecanoate ◽  
Androgen Replacement Therapy ◽  
Normal Men ◽  
Orally Active ◽  
Elevate Plasma ◽  
Androgen Levels

ABSTRACT Oral testosterone undecanoate (TU) in arachis oil has been evaluated with a view to its possible use as a means of androgen replacement therapy. A single 100 mg dose was found to elevate plasma androgen levels and urinary 17-ketosteroid excretion in 6 normal men. Ninety mg/day and 60 mg/day doses taken by a hypogonadal man resulted in sustained levels of androgen which appeared physiological when measured by radioimmunoassay without chromatography. However, upon separation of the steroids by chromatography it was found that much of the androgen present was in fact dihydrotestosterone not testosterone. Both TU and dihydrotestosterone undecanoate were detected in plasma by gas chromatography and it is suggested that the ester is absorbed as such from the intestine and the unesterified steroid subsequently released by hydrolysis. The convenience of oral administration, the resulting prolonged elevated plasma androgen levels and the probable lack of deleterious effects on the liver may render oral TU of value where androgen replacement therapy is indicated.

P4481NI956/QGC006, a potent orally active, brain-penetrating aminopeptidase A inhibitor prodrug for treating hypertension

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
M Keck ◽  
H De Almeida ◽  
D Compere ◽  
N Inguimbert ◽  
A Flahault ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Oral Administration ◽  
Sulfonic Acid ◽  
Plasma Sodium ◽  
High Dose ◽  
Hypertensive Rats ◽  
Arterial Blood ◽  
Angiotensin Iii ◽  
Aminopeptidase A ◽  
Orally Active

Abstract Background Brain renin-angiotensin system hyperactivity has been implicated in the development and maintenance of hypertension. We previously showed that aminopeptidase A (APA) generates in the brain, angiotensin III, which exerts a tonic stimulatory control over blood pressure in hypertensive rats. Thus, the central injection of the specific and selective APA inhibitor, EC33 ((3S)-3-amino-4-sulfanyl-butane-1-sulfonic acid), by blocking the formation of brain angiotensin III, normalizes blood pressure in experimental models of hypertension. Therefore, brain APA appears as a potential new therapeutic target for the treatment of hypertension. We then developed RB150/firibastat, a prodrug of EC33, able of inhibiting brain APA activity and decreasing blood pressure in hypertensive rats after oral administration. Purpose However, considering the high dose of orally active RB150/firibastat required to decrease BP in spontaneously hypertensive rats (SHR) (150 mg/kg) and deoxycorticosterone acetate-salt (DOCA-salt) (50 mg/kg) rats, the aim of our work was to develop new more potent APA inhibitor prodrugs with greater bioavailability for inhibiting brain APA activity. Methods We used a salt- and volume-dependent model of hypertension, the DOCA-salt rat. For in vivo assessments of brain APA activity, brains were collected 4 hours after the oral administration. A catheter was inserted into the right femoral artery to monitor mean arterial blood pressure in alert rats. We evaluated plasma arginine-vasopressin (AVP) levels by radioimmunoassay. Rats were individually housed in metabolic cages for urine and electrolyte output measurements. Results We report here the development of a new APA inhibitor prodrug, NI956/QGC006, obtained by the disulfide bridge-mediated dimerization of NI929 ((3S,4S)-3-amino-4-mercapto-6-phenyl-hexane-1-sulfonic acid). NI929 is 10 more efficient than EC33 at inhibiting recombinant mouse APA activity in vitro. Following oral administration at a dose of 4 mg/kg in conscious DOCA-salt rats, NI956/QGC006 normalized brain APA activity and induced a marked decrease in blood pressure of −44±13 mmHg four hours after treatment (p<0.001), sustained over ten hours (−21±12 mmHg, p<0.05). Moreover, NI956/QGC006 decreased plasma AVP levels, and increased diuresis and natriuresis, that may decrease blood pressure by reducing the size of the fluid compartment. Finally, NI956/QGC006 did not affect plasma sodium and potassium concentrations. Conclusions This study shows that NI956/QGC006 is a “best-in-class” central-acting APA inhibitor prodrug, belonging to the same drug class as RB150/firibastat, supporting the strategy of brain APA inhibition for hypertension treatment. Acknowledgement/Funding ANR (Agence Nationale de la Recherche) grant to Catherine Llorens-Cortes (LabCom CARDIOBAPAI) and Quantum Genomics financial support.

Colonisation of Germ-free Mice by Segmented Filamentous Bacteria after Oral Administration of Various Murine Intestinal Wall Preparations

1990 ◽  
Vol 3 (5) ◽  
pp. 281-284 ◽  
Author(s):  
H. L. B. M. Klaasen ◽  
J. P. Koopman ◽  
M. E. Van Den Brink ◽  
H. P. N. Van Wezel ◽  
P. M. Scholten ◽  
...  
Keyword(s):  
Oral Administration ◽  
Intestinal Wall ◽  
Filamentous Bacteria ◽  
Germ Free ◽  
Segmented Filamentous Bacteria

PROGESTATIONAL ACTIVITY OF STEREOISOMERIC PROGESTERONE-ANALOGUES FOLLOWING ORAL ADMINISTRATION IN AMENORRHOEA

1960 ◽  
Vol XXXV (II) ◽  
pp. 197-203 ◽  
Author(s):  
K.-G. Tillinger ◽  
E. Diczfalusy
Keyword(s):  
Side Effects ◽  
Oral Administration ◽  
Human Subject ◽  
Histological Appearance ◽  
Orally Active ◽  
Progesterone Analogues

ABSTRACT A stereoisomeric analogue of progesterone, 9β,10α-pregn-4-ene-3,20-dione (retro-progesterone) and a 6-dehydro derivative, 9β,10α-pregna-4,6-diene-3,20-dione (6-dehydro-retro-progesterone) were studied for their progestational activity in 26 artificial cycles induced in 17 amenorrhoic women.1 It was found that 6-dehydro-retro-progesterone is a highly potent orally active progestational agent in the human subject. Daily doses of 10 mg of this compound given orally for 10 days induced a definite secretory transformation of the endometrium. The histological appearance of the endometrium following treatment with this compound could not be distinguished from that seen in normal cycles. Both compounds studied were excellently tolerated; no toxic side-effects were observed.

Encapsulated egg deposition pattern of Schistosoma japonicum in the peritoneal cavity of mice

1994 ◽  
Vol 68 (2) ◽  
pp. 125-129 ◽  
Author(s):  
P.C. Fan ◽  
L.L. Lin
Keyword(s):  
Portal Vein ◽  
Schistosoma Japonicum ◽  
Peritoneal Cavity ◽  
Intestinal Wall ◽  
Deposition Pattern ◽  
Vein System ◽  
Egg Deposition ◽  
Worm Recovery ◽  
Mean Size ◽  
The Mean

AbstractThirty-four albino mice were each exposed to 20 cercariae of Schistosoma japonicum by the intraperitoneal or percutaneous route and killed after 60–127 days. The peritoneal cavity of each mouse was flushed and worms in the portal vein system were perfused with citrated saline. After sedimentation, washings were examined microscopically. Mature worms were only found in the portal vein system. The worm recovery rate was much higher by percutaneous infection (61.2%) than by intraperitoneal (37.1%). The encapsulated egg granulomas were observed either in the peritoneal cavity or on the intestinal wall; the mean number of encapsulated egg granulomas was also higher in the former (1.6) than in the latter (0.6). The average number of eggs per granuloma was very similar by both routes (10.7 and 11.4). The mean size of encapsulated egg granulomas (529 μm) was increased correspondingly with the number of eggs (range 181–985 μm). The percentage of viable eggs within the granulomas in the peritoneal cavity (77%) was much higher than those on the intestinal wall (18%). Encapsulated egg granulomas were usually ovoid although some had an irregular shape.

scholarly journals Possible Biomarkers in Blood for Crohn’s Disease: Oxidative Stress and MicroRNAs—Current Evidences and Further Aspects to Unravel

2016 ◽  
Vol 2016 ◽  
pp. 1-9 ◽  
Author(s):  
Inés Moret-Tatay ◽  
Marisa Iborra ◽  
Elena Cerrillo ◽  
Luis Tortosa ◽  
Pilar Nos ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Intestinal Wall ◽  
Inflammatory Disorder ◽  
Ros Production ◽  
Oxygen Species ◽  
Antioxidant Defences ◽  
Transmural Inflammation ◽  
Harmful Effects

Crohn’s disease (CD) is an inflammatory disorder characterised by a transmural inflammation of the intestinal wall. Although the physiopathology of the disease is not yet fully understood, it is clear that the immune response plays an important role in it. This hyperreactive immune system is accompanied by the presence of unregulated reactive oxygen species (ROS). These elements are modulated in normal conditions by different elements, including enzymes that function as antioxidant defences preventing the harmful effects of ROS. However, in CD there is an imbalance between ROS production and these antioxidant elements, resulting in oxidative stress (OxS) phenomena. In fact, now OxS is being considered more a potential etiological factor for Crohn’s disease rather than a concomitant effect in the disease. The persistence of the OxS can also be influencing the evolution of the disease. Furthermore, the epigenetic mechanisms, above all microRNAs, are being considered key elements in the pathogenesis of CD. These elements and the presence of OxS have also been linked to several diseases. We, therefore, describe in this review the most significant findings related to oxidative stress and microRNAs profiles in the peripheral blood of CD patients.

ANABOLIC, ANDROGENIC AND MYOTROPIC ACTIVITIES OF DERIVATIVES OF 7α-METHYL-19-NORTESTOSTERONE

1963 ◽  
Vol 43 (3) ◽  
pp. 399-411 ◽  
Author(s):  
Stanley C. Lyster ◽  
Gordon W. Duncan
Keyword(s):  
Oral Administration ◽  
Testosterone Propionate ◽  
Free Alcohol ◽  
Anabolic Agent ◽  
Androgenic Activity ◽  
Oral Activity ◽  
Derivatives Of

ABSTRACT Anabolic, myotropic and androgenic properties of a series of 7α=methyl-19-nortestosterone derivatives were compared using quantitative monkey anabolic and rat myotropic/androgenic assays. 7α-Methyl-19-nortestosterone acetate was found to be 6.5 times as potent an androgen as testosterone propionate, and 23 times as potent as a myotropic agent when parenterally administered. The cyclopentylpropionate ester, also more potent than testosterone propionate, possessed depot anabolic and androgenic activity. By oral administration, 7α,17α-dimethyl-19-nortestosterone was 14 times as potent as fluoxymesterone as an anabolic agent in monkeys and possessed a monkey anabolic/rat androgenic ratio of 7 : 1 relative to fluoxymesterone. The free alcohol parent of this series also had high oral activity and possessed a favorable anabolic/androgenic ratio.

Oral administration of tributyrin increases concentration of butyrate in the portal vein and prevents lipopolysaccharide-induced liver injury in rats

2011 ◽  
Vol 30 (2) ◽  
pp. 252-258 ◽  
Author(s):  
Makoto Miyoshi ◽  
Hiroe Sakaki ◽  
Makoto Usami ◽  
Norihito Iizuka ◽  
Katsuhito Shuno ◽  
...  
Keyword(s):  
Liver Injury ◽  
Portal Vein ◽  
Oral Administration

scholarly journals The Role of Protein Kinase Activators and ZFN in Reducing the Harmful Effects of Total Body Irradiation

2020 ◽  
Author(s):  
hana ahmd alahmd ◽  
sawsan madi ◽  
adnan ekhtiar
Keyword(s):  
Flow Cytometry ◽  
Radiation Therapy ◽  
Lymphatic System ◽  
Antiviral Treatment ◽  
Whole Body ◽  
Pathological Changes ◽  
Γ Rays ◽  
Total Body ◽  
Harmful Effects

Abstract ObjectiveAIDS patients are predisposed to develop certain tumors. Radiation therapy is one of the main treatments for cancer. However, exposure to ionizing radiation leads to defects in the lymphatic system. The cells with the highest sensitivity to radiation are the T lymphocytes. We aim to investigate the effect of irradiation on the ratio of CD4 to CD8, and to oppose this effect by using Bryostatin (B) and ZFN and ART (Anti-Retroviral Therapy). So Balb/C mice aged 6-8 weeks were whole-body irradiated with 1.5 Gy of γ-rays, was then mice were treated with ZFN, Bryostatin intraperitoneally. And orally Antiviral treatment. At the end of the study, CD4/CD8 was measured by flow cytometry.Results Irradiation caused significant pathological changes that led to a clear reversal of CD4/CD8 ratio significantly within the normal radiating group. there are no significant differences in CD4/CD8 ratio between all groups treated with ZFN+ X, Z+ B+ X, ART+ X and normal group.So our study suggests the effect of Bryostatin in protecting living organs that were exposed to irradiation in mice. ZFN cuts off both BAX and BAK, and thus decreases apoptotic proteins, reducing cell death.

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