scholarly journals Molecular weight as a factor in the excretion of monoquaternary ammonium cations in the bile of the rat, rabbit and guinea pig

1973 ◽  
Vol 136 (4) ◽  
pp. 967-978 ◽  
Author(s):  
Robin D. Hughes ◽  
Peter Millburn ◽  
R. Tecwyn Williams
Keyword(s):  
Molecular Weight ◽  
Bile Duct ◽  
Biliary Excretion ◽  
Guinea Pigs ◽  
Species Difference ◽  
Faecal Excretion ◽  
Molecular Weights ◽  
Pyridinium Cations ◽  
Monoquaternary Ammonium ◽  
Intact Rats

1. The excretion in the bile and urine of intraperitoneally injected14C-labelled monoquaternary ammonium or pyridinium cations was measured in bile-duct-cannulated rats (ten compounds) and in guinea pigs and rabbits (six compounds). 2. Seven of these, namely N-methylpyridinium, tetraethylammonium, trimethylphenylammonium, diethylmethylphenylammonium, methylphenyldipropylammonium, dibenzyldimethylammonium and tribenzylmethylammonium, were excreted largely unchanged in the bile and urine. 3. 3-Hydroxyphenyltrimethylammonium, 3-bromo-N-methylpyridinium and cetyltrimethylammonium were metabolized to an appreciable extent in the rat. 4. In intact rats intraperitoneally injected trimethylphenylammonium (mol.wt. 136) was excreted mainly in the urine, dibenzyldimethylammonium (mol.wt. 226) was excreted in roughly equal amounts in the urine and faeces, and tribenzylmethylammonium (mol.wt. 302) was excreted mainly in the faeces. The faecal excretion of these compounds corresponded to their biliary excretion in bile-duct-cannulated rats. About 3–4% of tribenzyl[14C]methylammonium was eliminated as14CO2. 5. In rats the extent of biliary excretion of four cations with molecular weights in the range 94–164 was less than 10% of the dose, whereas that of five cations with molecular weights 173–302 was greater than 10%. These results and other data from the literature suggested that the molecular weight needed for the biliary excretion of such cations to an extent of 10% or more of the dose was about 200±50. Studies with six cations in guinea pigs and rabbits suggest that this value applies also to these species. 6. The results suggest that the threshold molecular weight for the appreciable (>10%) biliary excretion of monoquaternary cations is different from that for anions (Millburn et al., 1967a; Hirom et al., 1972b). With rats, guinea pigs and rabbits, no significant species difference was noted, whereas with anions there is a marked species difference.

scholarly journals Biliary excretion in foreign compounds. Species difference in biliary excretion

1967 ◽  
Vol 105 (3) ◽  
pp. 1289-1293 ◽  
Author(s):  
M M Abou-el-Makarem ◽  
P Millburn ◽  
R L Smith ◽  
R T Williams
Keyword(s):  
Molecular Weight ◽  
Guinea Pig ◽  
Rhesus Monkey ◽  
Benzoic Acid ◽  
Biliary Excretion ◽  
Hippuric Acid ◽  
Species Differences ◽  
General Trend ◽  
Species Difference ◽  
Molecular Weights

1. The biliary excretion of injected [14C]aniline, [14C]benzoic acid, 4-amino-hippuric acid and 4-acetamidohippuric acid in six or eight species of animal (rat, dog, hen, cat, rabbit, guinea pig, rhesus monkey and sheep) was studied. 2. These compounds, with molecular weights in the range 93–236, are poorly excreted in the bile in all the species examined and, in effect, there is little significant species difference in the extent of their biliary excretion. 3. Compounds of higher molecular weight (355–495) were also studied, namely succinylsulphathiazole, [14C]stilboestrol glucuronide, sulphadimethoxine N1-glucuronide and phenolphthalein glucuronide. 4. With these compounds a clear species difference in the extent of biliary excretion was found, the rat, dog and hen being good excretors, the rabbit, guinea pig and monkey poor excretors, and the cat and sheep taking an intermediary position. 5. There was a general trend for biliary excretion to be higher in all species when the compounds were of higher molecular weight. 6. These results are discussed in their relation to species differences in drug metabolism.

scholarly journals Species variations in the threshold molecular-weight factor for the biliary excretion of organic anions

1972 ◽  
Vol 129 (5) ◽  
pp. 1071-1077 ◽  
Author(s):  
P. C. Hirom ◽  
P. Millburn ◽  
R. L. Smith ◽  
R. T. Williams
Keyword(s):  
Molecular Weight ◽  
Guinea Pig ◽  
Urinary Excretion ◽  
Intravenous Injection ◽  
Biliary Excretion ◽  
Guinea Pigs ◽  
Organic Anions ◽  
Female Rats ◽  
Weight Factor ◽  
Molecular Weights

1. The excretion in the bile and urine after intravenous injection of 16 organic anions having molecular weights between 355 and 752 was studied in female rats, guinea pigs and rabbits. 2. These compounds were mostly excreted unchanged, except for three of them, which were metabolized to a slight extent (<7% of dose). 3. The rat excreted all the compounds extensively (22–90% of dose) in the bile. 4. In guinea pigs four of the compounds with mol.wt. 355–403 were excreted in the bile to the extent of 7–16% of the dose, four with mol.wt. 407–465 to the extent of 25–44% and eight compounds with mol.wt. 479–752 to the extent of 44–100%. 5. In rabbits four compounds with mol.wt. 355–465 were excreted in the bile to the extent of 1–8% of the dose, two compounds with mol.wt. 479 and 495 to the extent of 24 and 22%, and six compounds with mol.wt. 505–752 to the extent of 31–94%. 6. These results, together with those of other investigations from this laboratory, are discussed and the conclusion is reached that there is a threshold molecular weight for appreciable biliary excretion (i.e. more than 10% of dose) of anions, which varies with species: about 325±50 for the rat, 400±50 for the guinea pig and 475±50 for the rabbit. 7. Anions with molecular weights greater than about 500 are extensively excreted in the bile of all three species. 8. That proportion of the dose of these compounds which is not excreted in the bile is excreted in the urine, and in the three species, bile and urine are complementary excretory pathways, urinary excretion being greatest for the compounds of lowest molecular weight and tending to decrease with increasing molecular weight. 9. Some implications of this interspecies variation in the molecular-weight requirement for extensive biliary excretion are discussed.

scholarly journals Biliary excretion of some diquaternary ammonium cations in the rat, guinea pig and rabbit

1973 ◽  
Vol 136 (4) ◽  
pp. 979-984 ◽  
Author(s):  
Robin D. Hughes ◽  
Peter Millburn ◽  
R. Tecwyn Williams
Keyword(s):  
Molecular Weight ◽  
Bile Duct ◽  
Guinea Pig ◽  
Biliary Excretion ◽  
Guinea Pigs ◽  
Significant Extent ◽  
Diquaternary Ammonium

1. The extent of the excretion in the bile and urine of the14C-labelled dications, diquat, paraquat, morfamquat, decamethonium and dimethyltubocurarine in bile-duct-cannulated rats, guinea pigs and rabbits was examined. 2. These compounds were excreted unchanged in bile and urine, except diquat, which was metabolized to a significant extent (18% of the dose) in the rabbit only. 3. The extent of the biliary excretion of diquat (mol wt. of ion 184), paraquat (186), decamethonium (258) and morfamquat (469) was less than 10% of the dose in the three species, whereas that of dimethlytubocurarine (653) was greater than 10% in the rat and rabbit but not in the guinea pig. 4. These results together with data from the literature suggest that the molecular weight at which the excretion of dications in the bile exceeds 10% of the dose is in the region of 500–600, which differs from the values for monocations (Hughes et al., 1973) and anions (Millburn et al., 1967; Hirom et al., 1972).

scholarly journals Biliary excretion of foreign compounds. Biphenyl, stilboestrol and phenolphthalein in the rat: molecular weight, polarity and metabolism as factors in biliary excretion

1967 ◽  
Vol 105 (3) ◽  
pp. 1275-1281 ◽  
Author(s):  
P Millburn ◽  
R L Smith ◽  
R T Williams
Keyword(s):  
Molecular Weight ◽  
Bile Acids ◽  
Biliary Excretion ◽  
Polar Group ◽  
Anionic Group ◽  
Molecular Weights ◽  
Minimum Value ◽  
Conjugated Bile Acids

1. The extent of biliary excretion of biphenyl, tetralin, stilboestrol and phenolphthalein was studied in the rat. 2. Biphenyl and its 4-hydroxy and 4,4′-dihydroxy derivatives are extensively excreted in the bile as glucuronides in amounts increasing in order of molecular weight. 3. Stilboestrol and its glucuronide are excreted almost quantitatively in the bile mainly as the monoglucuronide, as are also phenolphthalein and its glucuronide. 4. Tetralin is excreted to the extent of about 13% of the dose, mainly as ac-tetralyl glucuronides. 5. The results and those of Abou-El-Makarem, Millburn, Smith & Williams (1967) are discussed and it is concluded that the extent of biliary excretion of foreign compounds in rats depends on their molecular weight and their possessing a strongly polar anionic group. There appears to be a minimum value of this molecular weight below which little biliary excretion (i.e. not more than 5–10% of the dose) occurs. There is some latitude in the choice of this molecular weight, which is about 325±50. The necessary molecular weight and polar group can be acquired by metabolism. Above this minimum value biliary excretion increases with molecular weight. It is suggested that the mechanism of the biliary excretion of foreign compounds may be similar to that of conjugated bile acids, which are highly polar and whose molecular weights exceed 400.

scholarly journals Biliary excretion of amphetamine and methamphetamine in the rat

1972 ◽  
Vol 129 (1) ◽  
pp. 25-29 ◽  
Author(s):  
J. Caldwell ◽  
L. G. Dring ◽  
R. T. Williams
Keyword(s):  
Bile Duct ◽  
Biliary Excretion ◽  
Enterohepatic Circulation ◽  
Main Metabolite ◽  
Ring Hydroxylation ◽  
Intact Rats

1.14C-labelled amphetamine and methamphetamine were injected into rats cannulated at the bile duct under thiopentone anaesthesia and the output of their metabolites in urine and bile was determined. 2. With amphetamine, 69% of the14C was excreted in the urine and 16% in the bile in 24h. The main metabolite in bile was the glucuronide of 4-hydroxyamphetamine. The output of unchanged amphetamine was much greater in cannulated rats than in intact rats. 3. With methamphetamine, 54% of the14C appeared in the urine and 18% in the bile. The main metabolite in the bile was the glucuronide of 4-hydroxynorephedrine. The output of amphetamine, a metabolite of methamphetamine, was much greater in cannulated rats than in intact rats. 4. Evidence has been obtained for the enterohepatic circulation of certain amphetamine and methamphetamine metabolites in the rat. 5. Thiopentone anaesthesia appeared to inhibit the ring hydroxylation of amphetamine administered as such or formed as a metabolite of methamphetamine.

Investigation by HPLC of the Catabolism of Recombinant Tissue Plasminogen Activator in the Rat

1988 ◽  
Vol 60 (01) ◽  
pp. 107-112 ◽  
Author(s):  
Roy Harris ◽  
Louis Garcia Frade ◽  
Lesley J Creighton ◽  
Paul S Gascoine ◽  
Maher M Alexandroni ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Plasminogen Activator ◽  
Tissue Plasminogen Activator ◽  
Half Life ◽  
Recombinant Tissue Plasminogen Activator ◽  
Rat Plasma ◽  
High Molecular Weight Complex ◽  
Molecular Weights ◽  
Major Activity ◽  
Tissue Plasminogen

SummaryThe catabolism of recombinant tissue plasminogen activator (rt-PA) was investigated after injection of radiolabelled material into rats. Both Iodogen and Chloramine T iodination procedures yielded similar biological activity loss in the resultant labelled rt-PA and had half lives in the rat circulation of 1 and 3 min respectively. Complex formation of rt-PA was investigated by HPLC gel exclusion (TSK G3000 SW) fractionation of rat plasma samples taken 1-2 min after 125I-rt-PA injection. A series of radiolabelled complexes of varying molecular weights were found. However, 60% of the counts were associated with a single large molecular weight complex (350–500 kDa) which was undetectable by immunologically based assays (ELISA and BIA) and showed only low activity with a functional promoter-type t-PA assay. Two major activity peaks in the HPLC fractions were associated with Tree t-PA and a complex having a molecular weight of ̴ 180 kDa. HPLC fractionation to produce these three peaks at various timed intervals after injection of 125I-rt-PA showed each to have a similar initial rate half life in the rat circulation of 4-5 min. The function of these complexes as yet is unclear but since a high proportion of rt-PA is associated with a high molecular weight complex with a short half life in the rat, we suggest that the formation of this complex may be a mechanism by which t-PA activity is initially regulated and finally cleared from the rat circulation.

Permeability Enhancing and Chemotactic Activities of Lower Molecular Weight Degradation Products of Human Fibrinogen

1981 ◽  
Vol 45 (01) ◽  
pp. 090-094 ◽  
Author(s):  
Katsuo Sueishi ◽  
Shigeru Nanno ◽  
Kenzo Tanaka
Keyword(s):  
Molecular Weight ◽  
Degradation Products ◽  
Electron Microscopic Observation ◽  
Chemotactic Activity ◽  
Lower Molecular Weight ◽  
Electron Microscopic ◽  
Human Fibrinogen ◽  
Rabbit Skin ◽  
Molecular Weights ◽  
Active Fragments

SummaryFibrinogen degradation products were investigated for leukocyte chemotactic activity and for enhancement of vascular permeability. Both activities increased progressively with plasmin digestion of fibrinogen. Active fragments were partially purified from 24 hr-plasmin digests. Molecular weights of the permeability increasing and chemotactic activity fractions were 25,000-15,000 and 25,000 respectively. Both fractions had much higher activities than the fragment X, Y, D or E. Electron microscopic observation of the small blood vessels in rabbit skin correlated increased permeability with the formation of characteristic gaps between adjoining endothelial cells and their contraction.These findings suggest that lower molecular weight degradation products of fibrinogen may be influential in contributing to granulocytic infiltration and enhanced permeability in lesions characterized by deposits of fibrin and/or fibrinogen.

Toxicity of Heparinoids, with Special Reference to the Precipitation of Fibrinogen

1964 ◽  
Vol 12 (01) ◽  
pp. 232-261 ◽  
Author(s):  
S Sasaki ◽  
T Takemoto ◽  
S Oka
Keyword(s):  
Molecular Weight ◽  
Dextran Sulfate ◽  
Anticoagulant Activity ◽  
Molecular Structures ◽  
Severe Reaction ◽  
Clinical Use ◽  
Molecular Weights ◽  
Close Relationship

SummaryTo demonstrate whether the intravascular precipitation of fibrinogen is responsible for the toxicity of heparinoid, the relation between the toxicity of heparinoid in vivo and the precipitation of fibrinogen in vitro was investigated, using dextran sulfate of various molecular weights and various heparinoids.1. There are close relationships between the molecular weight of dextran sulfate, its toxicity, and the quantity of fibrinogen precipitated.2. The close relationship between the toxicity and the precipitation of fibrinogen found for dextran sulfate holds good for other heparinoids regardless of their molecular structures.3. Histological findings suggest strongly that the pathological changes produced with dextran sulfate are caused primarily by the intravascular precipitates with occlusion of the capillaries.From these facts, it is concluded that the precipitates of fibrinogen with heparinoid may be the cause or at least the major cause of the toxicity of heparinoid.4. The most suitable molecular weight of dextran sulfate for clinical use was found to be 5,300 ~ 6,700, from the maximum value of the product (LD50 · Anticoagulant activity). This product (LD50 · Anticoagulant activity) can be employed generally to assess the comparative merits of various heparinoids.5. Clinical use of the dextran sulfate prepared on this basis gave satisfactory results. No severe reaction was observed. However, two delayed reactions, alopecia and thrombocytopenia, were observed. These two reactions seem to come from the cause other than intravascular precipitation.

Molecular Weights of Factor VIII (AHF) and Factor IX (PTC) by Electron Irradiation

1962 ◽  
Vol 08 (02) ◽  
pp. 270-275 ◽  
Author(s):  
David L Aronson ◽  
John W Preiss ◽  
Michael W Mosesson
Keyword(s):  
Molecular Weight ◽  
Factor Viii ◽  
Electron Irradiation ◽  
Factor Ix ◽  
Molecular Weights

SummaryThe molecular weights of AHF (factor VIII) and of PTC (factor IX) have been estimated by their sensitivity to inactivation by 7 kilovolt electrons. The molecular weight of AHF was found to be 180 000 by this method and that of PTC was found to be 110 000.

scholarly journals Effects of Molecular Weight of Functionalized Liquid Butadiene Rubber as a Processing Aid on the Properties of SSBR/Silica Compounds

Polymers ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 850
Author(s):  
Donghyuk Kim ◽  
Byungkyu Ahn ◽  
Kihyun Kim ◽  
JongYeop Lee ◽  
Il Jin Kim ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Anionic Polymerization ◽  
High Performance ◽  
Crosslink Density ◽  
Functional Group ◽  
Vital Role ◽  
Butadiene Rubber ◽  
Molecular Weights ◽  
Mooney Viscosity ◽  
Silica Dispersion

Liquid butadiene rubber (LqBR) which used as a processing aid play a vital role in the manufacturing of high-performance tire tread compounds. However, the studies on the effect of molecular weight, microstructure, and functionalization of LqBR on the properties of compounds are still insufficient. In this study, non-functionalized and center-functionalized liquid butadiene rubbers (N-LqBR and C-LqBR modified with ethoxysilyl group, respectively) were synthesized with low vinyl content and different molecular weights using anionic polymerization. In addition, LqBR was added to the silica-filled SSBR compounds as an alternative to treated distillate aromatic extract (TDAE) oil, and the effect of molecular weight and functionalization on the properties of the silica-filled SSBR compound was examined. C-LqBR showed a low Payne effect and Mooney viscosity because of improved silica dispersion due to the ethoxysilyl functional group. Furthermore, C-LqBR showed an increased crosslink density, improved mechanical properties, and reduced organic matter extraction compared to the N-LqBR compound. LqBR reduced the glass transition temperature (Tg) of the compound significantly, thereby improving snow traction and abrasion resistance compared to TDAE oil. Furthermore, the energy loss characteristics revealed that the hysteresis loss attributable to the free chain ends of LqBR was dominant.

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