scholarly journals Evaluation of allergenic properties and immunotoxicity of Homeovox

2020 ◽  
pp. 45-48
Author(s):  
L. P. Kovalenko ◽  
E. A. Ivanova ◽  
A. S. Lapickaya ◽  
K. V. Korzhova ◽  
R. V. Zhurikov
Keyword(s):  
Immune Response ◽  
Oral Dose ◽  
Oral Administration ◽  
Single Oral Dose ◽  
Concanavalin A ◽  
Guinea Pigs ◽  
Allergic Reactions ◽  
F1 Hybrid ◽  
Dosage Range ◽  
Homeopathic Treatment

Homeovox, a multicomponent homeopathic treatment for laryngitis of various etiologies, was tested for allergenic properties and immunotoxicity.Methods. 80 male albino guinea pigs and 180 male СВА, C57BL/6 and F1 hybrid (CBAхС57BL/6) mice were used in the study. In order to assess immunotoxicity, Homeovox was administrated orally to mice for 14 days at doses of 100 mg/kg and 1 000 mg/kg. To assess the allergenic properties of Homeovox, albino guinea pigs were also given the drug at doses of 100 mg/kg and 1 000 mg/kg according to the standard immunization schedules.Results. Oral administration of Homeovox to mice for 14 days at doses of 100 mg/kg and 1 000 mg/kg did not cause significant changes in the main characteristics of immune response compared to controls. When assessing allergenicity, Homeovox at doses 100 mg/kg and 1 000 mg/kg administered according to the standard immunization schedules did not induce systemic anaphylaxis or active skin anaphylaxis in albino guinea pigs. The immunization of guinea pigs by Homeovox at the same doses in a mixture with Freund's complete adjuvant caused no delayed allergic reactions. Homeovox at a single oral dose of 1 000 mg/kg significantly decreased concanavalin A-induced inflammation in CBA mice by 58.4 %.Conclusion. Within the dosage range investigated, Homeovox does not induce immunotoxicity, immediate- or delayed-type allergic or pseudoallergic reactions.

scholarly journals The metabolism of 2,6-di-tert.-butyl-4-hydroxymethylphenol (Ionox 100) in the dog and rat

1965 ◽  
Vol 97 (1) ◽  
pp. 303-310 ◽  
Author(s):  
AS Wright ◽  
DAA Akintonwa ◽  
RS Crowne ◽  
DE Hathway
Keyword(s):  
Single Dose ◽  
Oral Dose ◽  
Oral Administration ◽  
Single Oral Dose ◽  
Individual Variation ◽  
Uronic Acid ◽  
Species Difference ◽  
Hydroxybenzoic Acid ◽  
Tert Butyl

1. A single oral dose of [(14)C]Ionox 100 to rats is almost entirely eliminated in 11 days: 89.1-107.2% of the (14)C is excreted and 0.29+/-0.02% of the dose is present in the carcass plus viscera after removal of the gut. Rats exhibit an individual variation in the elimination pattern, 15.6-70.8% of (14)C being excreted in the urine and 75.2-27.0% in the faeces during 11 days. 2. After the oral administration of [(14)C]Ionox 100 to dogs, 87.1-90.3% of the (14)C is excreted in the faeces and urine during 4 days. 3. Dogs and rats do not show a species difference in this pattern of elimination. 4. The rate of elimination from dogs and rats given a single dose of Ionox 100 is not affected by the size of the dose and the presence of triglyceride fat in the diet. 5. Ionox 100 is completely metabolized in dogs and rats: unchanged Ionox 100 is absent from the urine and faeces, and from the carcass when elimination is complete. In rats, 3,5-di-tert.-butyl-4-hydroxybenzoic acid accounts for 50-85% of a dose of Ionox 100 and (3,5-di-tert.-butyl-4-hydroxybenzoyl beta-d-glucopyranosid)uronic acid for 47-10%; in dogs, the unconjugated acid accounts for 85% and the ester glucuronide for 10-12%. 3,5-Di-tert.-butyl-4-hydroxyhippuric acid is not formed. Other metabolites, which have been detected in small quantity in the faeces and urine of animals dosed with Ionox 100, have not been identified. 6. 3,5-Di-tert.-butyl-4-hydroxybenzoic acid and (3,5-di-tert.-butyl-4-hydroxybenzoyl beta-d-glucopyranosid)uronic acid are also the major metabolites of Ionol (2,6-di-tert.-butyl-p-cresol) in rats. 7. The elimination of Ionox 100 metabolites from rats is faster than that of Ionol and its metabolites. Unlike Ionol, unchanged Ionox 100 could not be detected in the bodies of these animals.

scholarly journals Absorption, Metabolism, and Excretion of [14C]Viramidine in Humans

2006 ◽  
Vol 50 (7) ◽  
pp. 2368-2373 ◽  
Author(s):  
Chin-chung Lin ◽  
Christine Xu ◽  
Nanqun Zhu ◽  
Li-Tain Yeh
Keyword(s):  
Carboxylic Acid ◽  
Oral Dose ◽  
Oral Administration ◽  
Single Oral Dose ◽  
Blood Cells ◽  
Maximum Concentration ◽  
Metabolic Profile ◽  
Total Radioactivity ◽  
Time Curve ◽  
Concentration Time

ABSTRACT Absorption, metabolism, and excretion of [14C]viramidine, a prodrug of ribavirin, were studied in humans following a single oral dose (600 mg). Viramidine was rapidly absorbed, with a time to maximum concentration of the drug in plasma of 1.5 h. Viramidine and ribavirin accounted for only 4.3% and 42% of plasma area under the concentration-time curve (AUC) for radioactivity, respectively, indicating extensive conversion of viramidine to ribavirin, followed by further metabolism of ribavirin. The drug was largely trapped in red blood cells (RBC), with an RBC-to-plasma radioactivity AUC0-∞ ratio of 108. Excretion of total radioactivity in urine and feces accounted for 50.8% and 26.1% of the dose, respectively. The metabolic profile in urine (0 to 24 h) indicated that viramidine was excreted primarily as triazole carboxamide (TCONH2), triazole carboxylic acid nucleoside (TCOOH), and ribavirin with a small amount of unchanged viramidine, which each accounted for 64.1%, 17.0%, 15.7%, and 3.2% of urinary radioactivity, respectively. The amounts of unchanged viramidine (3.4% of dose) and ribavirin (10% of dose) in urine were small after oral administration of viramidine.

scholarly journals Differences in Tissue Distribution of Cyano–B12 and Hydroxo–B12 One Week after Oral Intake: An Experimental Study in Male Wistar Rats

Nutrients ◽  
2018 ◽  
Vol 10 (10) ◽  
pp. 1487
Author(s):  
Eva Greibe ◽  
Ole Nymark ◽  
Sergey Fedosov ◽  
Christian Heegaard ◽  
Ebba Nexo
Keyword(s):  
Experimental Study ◽  
Oral Dose ◽  
Oral Administration ◽  
Tissue Distribution ◽  
Single Oral Dose ◽  
Wistar Rats ◽  
Oral Intake ◽  
Diet Group ◽  
Male Wistar Rats

Foods contain natural vitamin B12 forms, such as hydroxo–B12 (HO–B12), whereas vitamin pills contain the synthetic cyano–B12 (CN–B12). Recent studies in rats showed different tissue distributions of CN–B12 and HO–B12 24 h after oral administration. Here, we investigate whether these differences are sustained or leveled out with time in both B12-deplete and -replete rats, thereby assessing if the two forms are equally good at maintaining a normal B12 status. Male Wistar rats were fed diets with low (n = 16) or high (n = 12) B12 content for 17 days. At day 10, the rats received a single oral dose of [57Co]-labeled CN–B12 or HO–B12 (n = 6 and n = 8, respectively, in each diet group). The rats were sacrificed on day 17 and endogenous B12 and [57Co]–B12 were measured in liver, kidney, and plasma. We found that the low-B12 diet introduced a B12-deplete state as judged from medians of endogenous B12 compared to rats on a (high-B12 diet): Plasma (565 (1410) pmol/L), liver (28.2 (33.2) pmol/g), and kidneys (123 (1300) pmol/g). One week after oral administration, the labeled B12 was distributed as follows: HO–B12 > CN–B12 (liver) and CN–B12 > HO–B12 (kidneys, plasma). The tissue/plasma ratios showed different equilibriums for labeled CN–B12 and HO–B12 in the B12-deplete and -replete groups. The equilibrium of endogenous B12 resembled [57Co]CN–B12 in replete rats but differed from both [57Co]CN–B12 and [57Co]HO–B12 in deplete rats. The data suggest long-term differences in tissue utilization of the two B12 forms and warrant further studies concerning the possible benefits of consuming HO–B12 instead of CN–B12 in oral B12 replacement.

scholarly journals Acute and 28-days subacute toxicity studies of Gαq-RGS2 signaling inhibitor

2021 ◽  
Vol 37 (1) ◽  
Author(s):  
Jayesh V. Beladiya ◽  
Anita A. Mehta
Keyword(s):  
Body Weight ◽  
Oral Dose ◽  
Oral Administration ◽  
Single Oral Dose ◽  
Hematological Parameters ◽  
Weight Ratio ◽  
Repeated Administration ◽  
Organ Damage ◽  
Synthetic Compound ◽  
Single Oral Administration

Abstract Background The aim of study was to evaluate the single oral dose and 28 day repeated oral administration toxicity profile of the synthetic compound Gαq-RGS2 signaling inhibitor, (1-(5-chloro-2-hydroxyphenyl)-3-(4-(trifluoromethyl)phenyl)-1 H-1,2,4-triazol-5(4 H)-one) as per OECD guideline 425 (2008a) and 407 (2008b), respectively. Results In acute toxicity study, a single oral dose administration of Gαq-RGS2 signaling inhibitor did not show any mortality at doses of 5, 50, 300 and 2000 mg/kg within 24 h and 14 days. The treatment of Gαq-RGS2 signaling inhibitor at dose 10 and 100 mg/kg for 28 days did not show any mortality, significant changes in the increase of body weight, various organ damage markers, hematological parameters, relative organ/body weight ratio and microscopic anatomical texture of essential organs as compared to vehicle and normal control. Conclusions A single oral administration of Gαq-RGS2 signaling inhibitor up to dose of 2000 mg/kg in mice and repeated administration of Gαq-RGS2 signaling inhibitor at higher dose 100 mg/kg for 28 days in the rats is safe.

Mass balance, pharmacokinetics, and metabolism of [14C] brivanib (BMS-582664), prodrug of BMS-540215, in subjects with advanced or metastatic solid tumors

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 3566-3566
Author(s):  
R. Ganapathi ◽  
T. Mekhail ◽  
C. Wu ◽  
B. Fischer ◽  
J. Gong ◽  
...  
Keyword(s):  
Oral Dose ◽  
Oral Administration ◽  
Single Oral Dose ◽  
Solid Tumors ◽  
Kinase Inhibitor ◽  
Total Radioactivity ◽  
Open Label ◽  
Single Dose Study ◽  
Brivanib Alaninate ◽  
Dose Study

3566 Background: Brivanib alaninate (BMS-582664, B) is an oral prodrug of BMS-540215, a dual tyrosine kinase inhibitor of VEGFR and FGFR signaling pathways which are important for angiogenesis and tumor growth. The recommended phase II/III dose of B is 800 mg daily. Methods: A two-part, open-label, single-dose study was conducted in subjects with advanced or metastatic solid tumors. Part A represented the period for assessment of the pharmacokinetics (PK), metabolism, and elimination of B, In part A, subjects received a single oral dose of 800 mg [14C]-labeled B containing 100 μCi of total radioactivity (0.125 μCi/mg). Blood was collected at selected time points for analyses of PK, biotransformation, and total radioactivity over a 10-day period. Complete urinary and fecal output was collected over the 10-day period or until discharge, and analyzed for total radioactivity and biotransformation. Part B began when subjects completed Part A. Part B subjects received B administered orally at a dose of 800 mg once daily starting on approximately Day 15 to 17 of study. Subjects continued in this study until disease progression or unacceptable toxicity. Results: 4 subjects (2 NSCLC, 1 ovarian, 1 renal cell carcinoma) were treated with B in both parts A & B. B was tolerable with few G3/4 AEs (increased fatigue, 1 event, cognitive disturbance, 1 event). The results revealed that B is completely converted to active moiety, BMS-540215, after oral administration. BMS-540215 is extensively metabolized in humans. Elimination is primarily via the feces. Following a single oral dose of [14C]-labeled B, approximately 12% and 82% of the administered radioactivity was recovered in the urine and feces, respectively, within 10 days. BMS-540215 accounted for 0.00% and 7.4% of the administered dose in urine and feces, respectively, with the remainder of the dose being minor metabolites. The mean terminal t1/2 of BMS-540215 was 14 hours. Conclusions: After oral administration of single 800 mg oral doses of [14C] B, BMS-540215 was found to be the major active circulating moiety in plasma (22.5%). BMS-540215 is primarily eliminated via metabolism. [14C]-labeled B formulation was well tolerated with no AEs leading to the discontinuation of any subject. [Table: see text]

scholarly journals PHARMACOKINETIC COMPARISON OF MONTELUKAST SODIUM FORMULATIONS AFTER A SINGLE ORAL DOSE IN HEALTHY GUINEA PIGS

2019 ◽  
pp. 165-169
Author(s):  
NEELAM SINGH ◽  
Giriraj T Kulkarni ◽  
Yatendra Kumar ◽  
GIRIRAJ T KULKARNI
Keyword(s):  
Plasma Concentration ◽  
Oral Dose ◽  
Single Oral Dose ◽  
Guinea Pigs ◽  
Elimination Rate ◽  
Pharmacokinetic Parameters ◽  
Time Data ◽  
Concentration Time ◽  
Montelukast Sodium ◽  
Significant Difference

Objective: Pharmacokinetic evaluation of montelukast sodium chronomodulated capsules (sustained-release solid dispersion of drug enclosed in pH-sensitive film-coated hard gelatin shell) and marketed tablets has been carried out in this study. Methods: A single oral dose of prepared capsules and marketed conventional tablets was administered in healthy male Dunkin-Hartley albino guinea pigs. Blood samples were collected at different time intervals and plasma concentration of drug was determined by reversed-phase high-performance liquid chromatography. Different pharmacokinetic parameters were assessed from plasma drug concentration-time profile by one-compartment model, first-order kinetics. Results: Pharmacokinetic parameters such as time to reach maximum concentration, elimination rate constant, elimination half-life, and mean residence time data indicates that drug release from chronomodulated capsules is significantly prolonged with initial release lag time of 3.5–4 h in comparison with marketed conventional tablets. However, maximum drug plasma concentration, area under the concentration-time curve, and apparent volume of distribution values show non-significant difference between capsules and marketed tablets. Conclusion: The findings specified that capsules were providing time controlled delivery of drug at a desired rate for prolonged time, which may be helpful for the prevention of episodic attack of asthma in early morning hours.

Humoral and cellular immune response to a crude exo-antigen and purified keratinase of Microsporum canis in experimentally infected guinea pigs

1999 ◽  
Vol 37 (2) ◽  
pp. 123-129 ◽  
Author(s):  
B. R. Mignon ◽  
T. Leclipteux ◽  
CH. Focant ◽  
A. J. Nikkels ◽  
G. E. PIErard ◽  
...  
Keyword(s):  
Immune Response ◽  
Cellular Immune Response ◽  
Guinea Pigs ◽  
Microsporum Canis ◽  
Cellular Immune

A Rapid (48 hours) Thyroid Suppression Test using a Single Oral Dose of 100 of Triiodothyronine

1973 ◽  
Vol 12 (03) ◽  
pp. 218-224
Author(s):  
Elli Lakka - Papadodima ◽  
Constantin Ntalles ◽  
Denis Ikkos
Keyword(s):  
Oral Dose ◽  
Single Oral Dose ◽  
Suppression Test

Des mesurages répétés de la fixation thyroïdienne de 10 minutes du 132I injecté intraveineusement on été effectués sur 55 malades euthyroïdiens sans et avec goitre et sur 16 malades hyperthyreoïdiens par 4 jours consécutifs. Immédiatement après le premier mesurage tous les malades recevaient une dose unique oral de 100 μg de Triiodothyronine (T3). Les valeurs de fixation 24, 48 et 72 heures après le T3 (moyen ± déviation standard) étaient de 75 ± 1,7, 64 ± 1,8, et 67 ± 1,9 dans le groupe euthyroïdien et le 106 ± 2,6, 104 ± 2,2 et 108 ± 4,0 dans le groupe hyperthyroïdien, exprimés en pourcentage du groupe controle. 48 heures après T3 tous les personnes euthyroïdiens, sauf une, avaient des valeurs en dessous de 88% tandis que la valeur la plus basse des personnes hyperthyroïdiens ce jour était de 93%. La séparation des valeurs 48 heures des deux groupes était complète après avoir respecté l’influence de la première fixation sur la valeur 48 heures. On peut donc supposer q’un test thyroïdien de suppression utilisable en clinique peut-être effectué en 48 heures après une administration oral de 100 μg de T3 et mesurage de la fixation 10 minutes après l’injection du radioisotope.

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