ELIMINATION AND METABOLISM OF 6-CHLORO-17α-HYDROXY-16-METHYLENE-4,6-PREGNADIENE-3,20-DIONE ACETATE AND ITS ANALOGUES IN RATS

1971 ◽  
Vol 66 (2) ◽  
pp. 303-316
Author(s):  
Z. Čekan ◽  
O. Horešovský
Keyword(s):  
Half Life ◽  
Isotope Analysis ◽  
Polar Compounds ◽  
Total Radioactivity ◽  
Acetoxy Group ◽  
Total Recovery ◽  
The Individual ◽  
Oral Doses ◽  
Layer Chromatography ◽  
Highly Polar Compounds

ABSTRACT The recovery of radioactivity in the urine, faeces and carcasses following single oral doses of [4-14C] progesterone, 17α-hydroxyprogesterone [2-14C] acetate (14C-AP), 16-methylene-6-dehydro-17α-hydroxyprogesterone [2-14C] acetate (14C-MAP), 6-bromo-16-methylene-6-dehydro17α-hydroxyprogesterone [2-14C] acetate (14C-BrMAP), 6-[36Cl] chloro-16-methylene-6-dehydro-17α-hydroxyprogesterone acetate (36Cl-ClMAP) and 6-chloro-16-methylene-6-dehydro-17α-hydroxyprogesterone [2-14C]-acetate (14C-ClMAP), respectively, was followed during 4–11 days. The total recovery was almost 100 per cent in all the compounds bearing the 17α-[14C] acetoxy group (AP, MAP, ClMAP, BrMAP). Comparison of 14C-ClMAP and 36Cl-ClMAP revealed that about 25 per cent of the administered radioactivity is eliminated in the urine in the form of desacetylated metabolites. However, most of the liberated acetic acid is not exspired, but is probably bound in an unknown form in the organism and excreted in the faeces. The half-life of 36Cl-ClMAP is longer than that of the steroids labelled with 14C in the 17α-acetoxy group (14C-ClMAP, 14C-BrMAP, 14C-MAP, 14C-AP). This fact can be accounted for by a prolonged elimination of desacetylated metabolites. The elimination in the urine of individual compounds was studied with ClMAP, AP, and MAP, the former two compounds being analyzed by double isotope analysis, the last one by single-label technique. The half-life of the individual compounds is shorter than that of the total radioactivity. This indicates that the individual compounds are eliminated faster than most of their metabolites. From the amount of unchanged steroids in the urine (related to the total radioactivity) it is apparent that ClMAP is metabolized less than AP, with MAP probably in an intermediate position. This correlates well with the biological activity of the compounds studied. A preliminary study showed that following the administration of 14C-ClMAP a major portion of the radioactivity was found in both the urine and faeces in a non-conjugated, mostly neutral form. The majority of the neutral metabolites consisted of highly polar compounds. None of the metabolites separated by thin-layer chromatography, however, could be identified.

Pharmacokinetics and Excretion of 14C-Labeled Polyethylene Glycol (60 kDa) in Rats

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 1473-1473 ◽  
Author(s):  
Andreas Baumann ◽  
Thomas Schwarz ◽  
Dietrich Seidel ◽  
Frank Hucke ◽  
Wolfram Steinke ◽  
...  
Keyword(s):  
Intravenous Administration ◽  
Half Life ◽  
Pediatric Population ◽  
Total Radioactivity ◽  
Total Recovery ◽  
Safety Issues ◽  
Animal Body ◽  
Elimination Half ◽  
Cumulative Excretion ◽  
Single Intravenous Administration

Abstract Introduction: Although there is no evidence for PEG-related safety issues with PEGylated proteins in the clinic, questions relating to the pharmacokinetics including disposition and excretion of PEG are being raised more frequently by health authorities nowadays, particularly for PEGylated proteins used chronically and/or in the pediatric population (http://www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2012/11/WC500135123.pdf).BAY 94-9027, a B-domain–deleted recombinant FVIII with a 60-kDa branched PEG molecule attached via a maleimide linker to an amino acid using site-specific PEGylation, is in clinical development for acute and prophylactic intravenous treatment of hemophilia A. The objective of this study was to investigate the pharmacokinetics and excretion of radioactivity (unchanged compound and radioactive metabolites) after single intravenous administration of 14C-labeled BAY 1025662 (cysteine linker-[60-kDa] PEG part of BAY 94-9027 with the 14C label covalently integrated in the linker) in male Wistar rats. Methods: The administered dose was 11 mg/kg body weight related to BAY 1025662 (approximated human lifetime dose of PEG 60 kDa resulting from treatment with BAY 94-9027). The concentrations and amounts of radioactivity in urine, feces, blood, plasma, and selected organs and tissues were investigated in order to determine the excretion via urine and feces, and the pharmacokinetics of total radioactivity and radioactive residues in the animal body. Results: After single intravenous administration of 14C-BAY 1025662 to rats, a fast initial elimination of 14C radioactivity was observed; 63.2% of administered radioactivity was excreted within the first 24 hours (51.4% in urine, 11.8% in feces). Up to day 7, 75.6% of administered radioactivity was excreted predominantly via urine. The balance/recovery of radioactivity on day 7 amounted to 99.0% in relation to the administered radioactive dose. The radioactive residue in the animals amounted to 23.4% of administered dose. The majority of the residual radioactivity was recovered in the carcass and skin, followed by liver and kidneys. The excretion of radioactivity continued at steadily decreasing levels until the end of the study. The daily radioactivity excretion decreased from 2.1% at 72 hours to 0.013% of dose at 6 months after administration of 14C-BAY 1025662. The cumulative excretion of radioactivity via urine and feces was calculated (partly interpolated) to 92.2% of the administered radioactive dose by the end of the experiment on day 168 (74.5% via urine, 17.4% via feces, and 0.294% recovered in the cage wash). The radioactivity was continuously albeit slowly eliminated from the investigated organs and tissues. The elimination half-life of radioactivity was 26 and 23 days in blood and plasma, respectively. The corresponding elimination half-lives of radioactivity were 35, 41, and 31 days in the liver, carcass, and skin, respectively. Radioactivity elimination from kidneys was biphasic with a terminal half-life of 92 days. The radioactive residues in the animals excluding the gastrointestinal tract decreased during the study from 22.5% on day 7 to 1.79% of dose at the end of the study on day 168. There was no indication for any retention or irreversible binding of radioactivity in the animal body. The total recovery of radioactivity (cumulative excretion plus residues in the animals) was 94% in relation to the administered dose at the end of the experiment on day 168. Conclusions: In this study, nearly complete excretion of the 60-kDa PEG molecule (measured as total radioactivity) could be observed, with a fast initial elimination in the first few days and a subsequent considerably slower process until the end of the observation period (6 months). These results are in agreement with recently proposed fast and slow processes for the renal excretion of large PEG and PEG proteins (Baumann, A. et al. Drug Discov Today. 2014:[Epub ahead of print, http://dx.doi.org/10.1016/j.drudis.2014.06.002]). Disclosures Baumann: Bayer Pharma AG: Employment. Schwarz:Bayer Pharma AG: Employment. Seidel:Bayer Pharma AG: Employment. Hucke:Bayer Pharma AG: Employment. Steinke:Bayer Pharma AG: Employment. Buehner:Bayer Pharma AG: Employment.

DES-AA Fibrin Clearance In Healthy Human Subjects

1981 ◽  
Author(s):  
F Brosstad ◽  
T Harrbora ◽  
B Holm ◽  
H C Godal ◽  
P Kierulf
Keyword(s):  
Half Life ◽  
Human Subjects ◽  
Total Radioactivity ◽  
Test Subject ◽  
Healthy Human ◽  
Individual Molecular Species ◽  
Edta Plasma ◽  
Specific Receptors ◽  
The Individual ◽  
Decay Parameters

Plasma clearance of I125 des-AA fibrin mcncmers was studied in healthy subjects (N=7). Labelled mcnaners (fm), made fran labelled fibrinogen (F) in 2,5 M urea, pH 7,4 exposed to insoluble reptilase (Brosstad et al., Thrarto .Res. 13, 1978) vere solubilized upon addition to test-subject plasma, and subsequently injected. At intervals, citrated plasma samples ware tested for: I. Total radioactivity (Tr). II. Radioprecipitability (Rp) with trichloroacetic acid. III. Radioclottability (Rc) with plasmin-free thrcmbin (pH 6,3 1h). IV. Radiodistribution after ultrasentrifuga-ticn (Airfug, Beckmann) and V. Radiodistributicn in SDS-PAGE gels after electrophoresis of harvested EDTA-plasma clots, solubilized in urea-SDS.RESULTS: Prior to injection, plasma demonstrated: Rp = 100 %, Rc = 94 %, single peak ultracentrifuge pattern and 95 % of total radioactivity moving as F on SDS-gels. Almost identical results were obtained in all subjects. After 30 min., Tr had dropped to 50 % of Tr value at 5 min., being 10 % and 2 % after 420 min. and 48 h., correspondingly. A parallell drop in Rp and Rc scarcely noticeable at 10 min., reached a mininun of 30 % at 360 min; the Airfug and SDS-gel patterns substantiating these findings. Due to non-linearity on semilog. plots, a definite half-life of des-AA fibrin cannot be stated from decay parameters (Tr) alone, but metabolic data as outlined above (Rp, Rc, Airfug, SDS-elpho) suggest a half-life of 30-60 min .. In five subjects, I131-des-AA fibrin and I125-fibrinogen was injected simultaneously. Clearance rates characteristic of that of the individual molecular species were obtained. The extremely rapid elimination of fibrin ccnpared to that of fibrinogen suggests specific receptors on RES- cells to be involved.

Radiocarbon Dating and Dietary Stable Isotope Analysis of Kwaday Dän Ts'inchí

2007 ◽  
Vol 72 (4) ◽  
pp. 719-734 ◽  
Author(s):  
Michael P. Richards ◽  
Sheila Greer ◽  
Lorna T. Corr ◽  
Owen Beattie ◽  
Alexander Mackie ◽  
...  
Keyword(s):  
Radiocarbon Dating ◽  
Isotope Analysis ◽  
Human Remains ◽  
Isotopic Analysis ◽  
High Elevation ◽  
Bone Collagen ◽  
Contact Period ◽  
European Contact ◽  
Ams Dating ◽  
The Individual

We report here on the results of AMS dating and isotopic analysis of the frozen human remains named Kwaday Dän Ts'inchí and associated materials recovered from a glacier located in Northwest British Columbia, Canada in 1999. The isotopic analysis of bone collagen (bulk and single amino acids) from the individual indicates a strongly marine diet, which was unexpected given the location of this find, more than 100 km inland eroding out of a high elevation glacier; however, bulk hair and bone cholesterol isotopic values indicate a shift in diet to include more terrestrial foods in the year before death. The radiocarbon dating is not straightforward, as there are difficulties in determining the appropriate marine correction for the human remains, and the spread of dates on the associated artifacts clearly indicates that this was not a single use site. By combining the most recent date on a robe worn by Kwaday Dän Ts'inchi with direct bone collagen dates we conclude that the individual likely dates to between cal A.D. 1670 to 1850, which is in the pre-(or early) European contact period for this region.

Catacomb culture wagons of the Eurasian steppes

Antiquity ◽  
2014 ◽  
Vol 88 (340) ◽  
pp. 378-394 ◽  
Author(s):  
N.I. Shishlina ◽  
D.S. Kovalev ◽  
E.R. Ibragimova
Keyword(s):  
Stable Isotope ◽  
Isotope Analysis ◽  
Burial Mound ◽  
Careful Selection ◽  
Southern Russia ◽  
The Subject ◽  
The Individual ◽  
Wheeled Vehicles ◽  
Selection Of ◽  
Catacomb Culture

The origin and development of wheeled vehicles continues to fascinate today no less than when Stuart Piggott (1974) first wrote about the subject inAntiquity40 years ago. A growing number of examples from the steppes of southern Russia and Ukraine are providing new insights into the design and construction of these complex artefacts. A recent example from the Ulan IV burial mound illustrates the techniques employed and the mastery of materials, with careful selection of the kinds of wood used for the wheels, axles and other elements. Stable isotope analysis of the individual interred in this grave showed that he had travelled widely, emphasising the mobility of steppe populations.

Pharmacokinetics and Tissue Residues of Sulfathiazole and Sulfamethazine in Pigs

1994 ◽  
Vol 57 (9) ◽  
pp. 796-801 ◽  
Author(s):  
LIEVE S. G. VAN POUCKE ◽  
CARLOS H. VAN PETEGHEM
Keyword(s):  
Intravenous Injection ◽  
Half Life ◽  
Intramuscular Injection ◽  
Compartment Model ◽  
Absolute Bioavailability ◽  
Pharmacokinetic Parameters ◽  
Tissue Concentrations ◽  
Single Intravenous Injection ◽  
The Individual ◽  
Residue Study

The plasma pharmacokinetics and tissue penetration of sulfathiazole (ST) and sulfamethazine (SM) after intravenous and intramuscular injection in pigs were studied. Following a single intravenous dose of 40 mg ST/kg of bodyweight or 80 mg SM/kg of bodyweight, the plasma ST and SM concentrations were best fitted to a two-compartment model. The areas under the curve were 447 ± 39 and 1485 ± 41 mg/h/L, clearances were 0.090 ± 0.007 and 0.054 ± 0.001 L/kg/h, volumes of distribution were 1.16 ± 0.16 and 0.77 ± 0.06 L/kg, half-lifes in distribution phase were l.18 ± 0.57 and 0.23 ± 0.16 h and half-lifes in eliminations phase were 9.0 ± l.6 and 9.8 ± 0.6 h. When the two compounds were administered simultaneously as a single intravenous injection, the pharmacokinetic parameters for ST were not significantly different. The values for SM show statistical differences for some important parameters: α, β and the AUC0–>∞ were significantly decreased and t1/2α, Vd and CIB were significantly increased. It can be concluded that after a single intravenous injection of 40 mg/kg, sulfathiazole has a high tl/2β resulting in higher tissue concentrations. This half-life, which is higher than what is reported in the literature, is not influenced by the simultaneous presence of sulfamethazine. The tl/2β for sulfamethazine after a single intravenous injection of 80 mg/kg is comparable to the data from the literature and is not influenced by the presence of sulfathiazole. Sulfathiazole and SM were also administered simultaneously as an intramuscular injection to healthy pigs at a dosage of 40 and 80 mg/kg bodyweight. Pharmacokinetic experiments were conducted on three pigs. From this pharmacokinetic study it can be concluded that upon a single intramuscular administration of 40 mg/kg of ST and 80 mg/kg of SM the absolute bioavailability in pigs is 0.92 ± 0.04 for ST and l.01 ± 0.07 for SM. Six pigs received five intramuscular im) injections as a single dose of ST and SM every 24 h for five consecutive days for the residue study. The pigs were slaughtered at different times after the last dose was given and samples were taken from various tissues and organs. Concentrations were determined by a microbiological method and a HPTLC method. No edible tissue contained more than 100 μg/kg of the individual sulfonamides after 10 days of withdrawal. It means that adult animals which have a shorter half-life and thus lower tissue concentrations will certainly meet the economic community EC) maximum residue limits after a 10 days withdrawal period.

WCOT Capillary Column GC/FT-IR and GC/MS for Identifying Toxic Organic Pollutants

1981 ◽  
Vol 35 (5) ◽  
pp. 469-472 ◽  
Author(s):  
Kenneth H. Shafer ◽  
M. Cooke ◽  
F. DeRoos ◽  
R. J. Jakobsen ◽  
O. Rosario ◽  
...  
Keyword(s):  
Capillary Column ◽  
Polar Compounds ◽  
Priority Pollutants ◽  
Library Search ◽  
Ft Ir ◽  
Complementary Nature ◽  
Standard Solution ◽  
The Individual ◽  
Nonpolar Compounds ◽  
Combined Data

The combined data of high-resolution chromatography GC/FT-IR and GC/MS is used to identify a standard solution of priority pollutants. Identifications made by the individual library search routines are compared and an improvement is demonstrated in the number of identifications with the combined GC/FT-IR and GC/MS data. Both GC/FT-IR and GC/MS separations are performed on WCOT capillary columns. This provides the best separation possible and also permits fast and efficient comparison of spectral data when separations are performed on the same type of column. GC/FT-IR shows more selectivity for polar compounds, whereas GC/MS selectivity favors nonpolar compounds. These selectivity differences emphasize the complementary nature of (and the need for) both GC/FT-IR and GC/MS information.

scholarly journals Chiral Separation of Diastereoisomers of Cefuroxime Axetil by High-Performance Thin-Layer Chromatography

2010 ◽  
Vol 93 (3) ◽  
pp. 771-777 ◽  
Author(s):  
Monika Dbrowska ◽  
Jan Krzek
Keyword(s):  
High Performance ◽  
High Sensitivity ◽  
Cefuroxime Axetil ◽  
Spectrometric Analysis ◽  
Good Separation ◽  
High Recovery ◽  
Cellulose Layers ◽  
The Individual ◽  
Layer Chromatography

Abstract Conditions for separation and determination of diastereoisomers of cefuroxime axetil by HPTLC on cellulose layers with densitometry were developed. A good separation of the constituents was achieved using a mobile phase composed of 1 aqueous -cyclodextrinmethanol (15 + 1, v/v). For detecting spots on the chromatograms, densitometric measurements were used at 285 nm. The method is characterized by high sensitivity; the LOD was 0.04 g/spot and LOQ was 0.11 g/spot for both forms of the cefuroxime axetil diastereoisomers. For the individual diastereoisomers, high recovery values from 96.63 to 104.16 were obtained. Identification of the diastereoisomers was performed by 1H-NMR spectrometric analysis.

Bioremediation of synthetic fatliquors under microaerobic condition

2016 ◽  
Vol 75 (5) ◽  
pp. 1118-1127 ◽  
Author(s):  
B. Umamaheswari ◽  
K. Priya ◽  
Rama Rajaram
Keyword(s):  
Oxygen Demand ◽  
Polar Compounds ◽  
Industrial Applications ◽  
Gas Chromatography Mass Spectrometry ◽  
Microaerobic Condition ◽  
Wide Range ◽  
End Products ◽  
Emulsifying Agent ◽  
Microaerobic Conditions ◽  
Layer Chromatography

Synthetic fatliquors are useful as a fatliquoring agent, flotation agent and emulsifying agent in a wide range of industrial applications such as leather, pharmacy and farm chemicals. These fatliquors remain recalcitrant to natural biota in existing treatment plants. In the present study, the isolated microaerophilic Serratia sp. HA1 strain CSMB3 is capable of utilizing structurally different fatliquors as the sole substrate for their growth under microaerobic conditions. Degradation of vegetable fatliquors was observed from 95 to 97% in terms of lipids, with the production of lipase at 72 h. Degradation of synthetic fatliquors was observed in terms of chemical oxygen demand from 85% to a minimum of 25%. It is in the order of sulfited/sulfated fatliquors > sulfochlorinated fatliquors > chlorinated fatliquors. A thin layer chromatography chromatogram confirmed the degradation of non polar fatliquor to polar compounds. Production of the red pigment prodigiosin in synthetic fatliquors enhanced the growth of the isolate. Fourier transform infrared spectroscopy (FTIR) confirmed the bioremediation of sulfochlorinated fatliquor into lipids and fatty acids and gas chromatography–mass spectrometry (GC-MS) results confirmed that alcohols and esters are the final end products. Thus the isolated strain CSMB3 may be used in the treatment of wastewaters containing vegetable and synthetic fatliquors.

scholarly journals Levers to Improve Antibiotic Treatment of Lambs via Drinking Water in Sheep Fattening Houses: The Example of the Sulfadimethoxine/Trimethoprim Combination

Antibiotics ◽  
2020 ◽  
Vol 9 (9) ◽  
pp. 561
Author(s):  
Aude A. Ferran ◽  
Marlène Z. Lacroix ◽  
Alain Bousquet-Mélou ◽  
Ivain Duhil ◽  
Béatrice B. Roques
Keyword(s):  
Drinking Water ◽  
Oral Bioavailability ◽  
Half Life ◽  
Plasma Concentrations ◽  
Oral Route ◽  
Disease Spread ◽  
Bacterial Diseases ◽  
Terminal Half Life ◽  
High Interindividual Variability ◽  
The Individual

To limit the spread of bacterial diseases in sheep fattening houses, antibiotics are often administered collectively. Collective treatments can be delivered by drinking water but data on the drug’s solubility in water or on plasma exposure of the animals are lacking. We first assessed the solubility of products containing sulfadimethoxine (SDM), associated or not with trimethoprim (TMP), in different waters. We then compared in lambs the SDM and TMP pharmacokinetic profiles after individual intravenous (IV) and oral administrations of SDM-TMP in experimental settings (n = 8) and after a collective treatment by drinking water with SDM-TMP or SDM alone in a sheep fattening house (n = 100 for each treatment). The individual water consumption during the collective treatments was also monitored to characterize the ingestion variability. We showed that TMP had a short terminal half-life and very low oral bioavailability, demonstrating that it would be unable to potentiate SDM by oral route. Conversely, SDM had a long terminal half-life of 18 h and excellent oral bioavailability. However, delivery by drinking water resulted in a very high interindividual variability of SDM plasma concentrations, meaning that although disease spread could be controlled at the group level, some individuals would inevitably be under- or over-exposed to the antibiotic.

Instability of Some TWchothecenes in Methanol

1986 ◽  
Vol 69 (5) ◽  
pp. 902-903 ◽  
Author(s):  
Ru-Dong Wei ◽  
Fun S Chu
Keyword(s):  
Thin Layer ◽  
Thin Layer Chromatography ◽  
Room Temperature ◽  
Early Stage ◽  
Acetoxy Group ◽  
Layer Chromatography

Abstract Stability of 8 trichothecenes stored in methanol at room temperature was studied by thin layer chromatography. Results indicate that the trichothecenes which bear an acetoxy group at both C3 and C4 are very susceptible to methanolysis. In the early stage, the acetoxy group at C3 is most favorable for the transesterification. All trichothecenes tested were transformed to several products after prolonged (22 days) exposure to methanol.

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