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 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 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 Afibrinogenemia and Thrombocytopenia in Guinea Pigs Following Injection of Echis Colorata Venom

Blood ◽  
1962 ◽  
Vol 20 (6) ◽  
pp. 735-749 ◽  
Author(s):  
JADWIGA RECHNIC ◽  
POLA TRACHTENBERG ◽  
JULIAN CASPER ◽  
CHAJA MOROZ ◽  
ANDRÉ DE VRIES
Keyword(s):  
Guinea Pig ◽  
Intravenous Injection ◽  
Guinea Pigs ◽  
Procoagulant Activity ◽  
Rabbit Serum ◽  
Factor V ◽  
Factor V Deficiency ◽  
Fibrinogenolytic Activity ◽  
Fraction I ◽  
Lethal Doses

Abstract Intravenous injection into the guinea pig of lethal doses of Echis colorata venom or of each of its two chromatographic fractions, separately, caused hemorrhage, afibrinogenemia, factor V deficiency and thrombocytopenia. Sublethal venom doses caused afibrinogenemia, factor V deficiency and thrombocytopenia in the absence of hemorrhage. Early intravascular clotting was observed following injection of high lethal doses of both whole venom and of procoagulant-containing fraction II, but not of fraction I which was devoid of procoagulant activity. The afibrinogenemia produced by fraction I was due to its fibrinogenolysin, whereas the afibrinogenemia produced by fraction II, which also had fibrinogenolytic activity, was due chiefly to its procoagulant. Anti-Echis colorata venom rabbit serum inhibited the fibrinogenolytic, the procoagulant and the thrombocytopenic activities of the venom.

scholarly journals The biliary excretion of anions of molecular weight 300-800 in the rat, guinea pig and rabbit

1971 ◽  
Vol 125 (2) ◽  
pp. 25P-26P ◽  
Author(s):  
F T Aziz ◽  
P C Hirom ◽  
P Millburn ◽  
R L Smith ◽  
R T Williams
Keyword(s):  
Molecular Weight ◽  
Guinea Pig ◽  
Biliary Excretion

scholarly journals QUANTITATIVE DISTRIBUTION OF PARTICULATE MATERIAL (MANGANESE DIOXIDE) ADMINISTERED INTRAVENOUSLY TO THE DOG, RABBIT, GUINEA PIG, RAT, CHICKEN, AND TURTLE

1921 ◽  
Vol 33 (2) ◽  
pp. 231-238 ◽  
Author(s):  
Charles C. Lund ◽  
Louis A. Shaw ◽  
Cecil K. Drinker
Keyword(s):  
Guinea Pig ◽  
Manganese Dioxide ◽  
Intravenous Injection ◽  
Guinea Pigs ◽  
Particulate Material ◽  
The Other ◽  
Quantitative Distribution

The distribution of manganese dioxide particles 1 hour following intravenous injection in cats, dogs, rabbits, guinea pigs, rats, chickens, and turtles is described. This distribution is remarkably constant for all the animals tested, except the cat, in which the injected material is practically equally divided between the lungs and liver. In the other animals the liver performs the main share of the work, and in the cat it has been shown that the liver after 12 hours accumulates the manganese which was formerly deposited in the lungs. The results are in harmony with experiments in which bacterial suspensions are employed for injection and confirm the suggestion previously made (2) that in the first handling of foreign particulate material the animal behaves similarly whether protein or inorganic injections are used.

scholarly journals Reversed passive anaphylaxis in the guinea-pig

1940 ◽  
Vol 40 (4) ◽  
pp. 377-395 ◽  
Author(s):  
M. van den Ende
Keyword(s):  
Guinea Pig ◽  
Intravenous Injection ◽  
Guinea Pigs ◽  
Anaphylactic Shock ◽  
Cellular Mechanism ◽  
Rabbit Serum ◽  
Rabbit Antibody ◽  
Egg Albumin

Attempts to demonstrate reversed passive anaphylaxis in the guinea-pig with crystalline egg albumin as sensitizing antigen have been uniformly negative.When purified anti-pneumococcal antibody globulin was used as sensitizing antigen, reversed anaphylactic shock could be elicited in guinea-pigs by the intravenous injection of precipitins for the antibody globulin.The mild reactions which could be elicited when the total globulins from the serum of normal rabbits were used as sensitizing antigen are probably dependent on the presence of small amounts of y globulin.Reversed passive anaphylaxis, like direct anaphylaxis, is dependent on a cellular mechanism, and the success of experiments in which rabbit antibody globulin was used as sensitizing antigen depends on the acceptability of the antibody to the cells of the guinea-pig's tissues.Antigenic differences between antibody globulins and total normal globulins from rabbit serum are noted.

scholarly journals The molecular-weight factor in the biliary excretion of quaternary ammonium cations

1972 ◽  
Vol 128 (4) ◽  
pp. 144P-144P ◽  
Author(s):  
R D Hughes ◽  
P Millburn ◽  
R L Smith ◽  
R T Williams
Keyword(s):  
Molecular Weight ◽  
Biliary Excretion ◽  
Quaternary Ammonium ◽  
Weight Factor ◽  
Quaternary Ammonium Cations

scholarly journals THE CONDITIONS AND CHARACTERS OF THE IMMUNITY PRODUCED IN THE GUINEA PIG BY INSTILLATION OF HORSE SERUM INTO THE NOSE

1916 ◽  
Vol 24 (1) ◽  
pp. 69-86 ◽  
Author(s):  
Henry Sewall ◽  
Cuthbert Powell
Keyword(s):  
Infectious Disease ◽  
Guinea Pig ◽  
Intravenous Injection ◽  
Guinea Pigs ◽  
Subcutaneous Injection ◽  
Marked Effect ◽  
Horse Serum ◽  
Normal Animal ◽  
Set Up ◽  
Resting Period

1. Normal guinea pigs treated by four to six instillations of horse serum into the nose on alternate days become either hypersensitive or refractory to an intravenous injection of 0.38 cc. of serum given 16 days after the last instillation. If the amount of serum in each instillation is as much as 0.2 cc., anaphylactic death is caused by the toxic injection. If the amount of serum in each instillation is reduced to 0.04 cc. the first intravenous injection is without marked effect, and a second injection and subsequent injections of the same amount of antigen are well tolerated in about half the cases. 2. The effect produced by a given dose of serum, whether protective or anaphylactic, depends probably upon the extent of contact with the mucous membrane of the nose. 3. Guinea pigs which, after nasal treatment, have become tolerant to a definite maximum intravenous injection of the antigen appear to increase the degree of their tolerance, at least up to a resting period of more than 4 months. The same does not hold in animals immunized by the peritoneal route. 4. The first two or three instillations of a series probably determine the biologic character, whether of hypersensitiveness or hyposensitiveness, of reaction towards the serum. 5. It is probable that, contrary to the case in parenteral sensitization, hypersensitiveness and protection, respectively, set up by nasal instillations and not followed by parenteral injections, gradually disappear in about 50 to 100 days. 6. We have failed in attempts to eliminate hypersensitiveness, due to subcutaneous injection of serum, by nasal instillations which would protect the normal animal from the development of anaphylaxis. 7. It is suggested that the principles of prophylaxis evolved under these relatively simple conditions should be applied in the study of infectious disease.

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.

Sign in / Sign up

Export Citation Format

Share Document