scholarly journals The metabolic fate of amphetamine in man and other species

1970 ◽  
Vol 116 (3) ◽  
pp. 425-435 ◽  
Author(s):  
L. G. Dring ◽  
R. L. Smith ◽  
R. T. Williams
Keyword(s):  
Guinea Pig ◽  
Rhesus Monkey ◽  
Benzoic Acid ◽  
Acid Hydrolysis ◽  
Rhesus Monkeys ◽  
Methyl Ketone ◽  
Metabolic Fate ◽  
Unchanged Drug ◽  
Main Metabolite ◽  
Acid Labile

1. The fate of [14C]amphetamine in man, rhesus monkey, greyhound, rat, rabbit, mouse and guinea pig has been studied. 2. In three men receiving orally 5mg each (about 0.07mg/kg), about 90% of the 14C was excreted in the urine in 3–4 days. About 60–65% of the 14C was excreted in 1 day, 30% as unchanged drug, 21% as total benzoic acid and 3% as 4-hydroxyamphetamine. 3. In two rhesus monkeys (dose 0.66mg/kg), the metabolites excreted in 24h were similar to those in man except that there was little 4-hydroxyamphetamine. 4. In greyhounds receiving 5mg/kg intraperitoneally the metabolites were similar in amount to those in man. 5. Rabbits receiving 10mg/kg orally differed from all other species. They excreted little unchanged amphetamine (4% of dose) and 4-hydroxyamphetamine (6%). They excreted in 24h mainly benzoic acid (total 25%), an acid-labile precursor of 1-phenylpropan-2-one (benzyl methyl ketone) (22%) and conjugated 1-phenylpropan-2-ol (benzylmethylcarbinol) (7%). 6. Rats receiving 10mg/kg orally also differed from other species. The main metabolite (60% of dose) was conjugated 4-hydroxyamphetamine. Minor metabolites were amphetamine (13%), N-acetylamphetamine (2%), norephedrine (0.3%) and 4-hydroxynorephedrine (0.3%). 7. The guinea pig receiving 5mg/kg excreted only benzoic acid and its conjugates (62%) and amphetamine (22%). 8. The mouse receiving 10mg/kg excreted amphetamine (33%), 4-hydroxyamphetamine (14%) and benzoic acid and its conjugates (31%). 9. Experiments on the precursor of 1-phenylpropan-2-one occurring in rabbit urine suggest that it might be the enol sulphate of the ketone. A very small amount of the ketone (1–3%) was also found in human and greyhound urine after acid hydrolysis.

scholarly journals Metabolism of [14C]methamphetamine in man, the guinea pig and the rat

1972 ◽  
Vol 129 (1) ◽  
pp. 11-22 ◽  
Author(s):  
J. Caldwell ◽  
L. G. Dring ◽  
R. T. Williams
Keyword(s):  
Guinea Pig ◽  
Benzoic Acid ◽  
Methyl Ketone ◽  
Species Differences ◽  
Human Subjects ◽  
Main Reaction ◽  
Unchanged Drug ◽  
Aromatic Hydroxylation ◽  
Dose Dependent ◽  
Acid Labile

1. The metabolites of (±)-2-methylamino-1-phenyl[1-14C]propane ([14C]methamphetamine) in urine were examined in man, rat and guinea pig. 2. In two male human subjects receiving the drug orally (20mg per person) about 90% of the14C was excreted in the urine in 4 days. The urine of the first day was examined for metabolites, and the main metabolites were the unchanged drug (22% of the dose) and 4-hydroxymethamphetamine (15%). Minor metabolites were hippuric acid, norephedrine, 4-hydroxyamphetamine, 4-hydroxynorephedrine and an acid-labile precursor of benzyl methyl ketone. 3. In the rat some 82% of the dose of14C (45mg/kg) was excreted in the urine and 2–3% in the faeces in 3–4 days. In 2 days the main metabolites in the urine were 4-hydroxymethamphetamine (31% of dose), 4-hydroxynorephedrine (16%) and unchanged drug (11%). Minor metabolites were amphetamine, 4-hydroxyamphetamine and benzoic acid. 4. The guinea pig was injected intraperitoneally with the drug at two doses, 10 and 45mg/kg. In both cases nearly 90% of the14C was excreted, mainly in the urine after the lower dose, but in the urine (69%) and faeces (18%) after the higher dose. The main metabolites in the guinea pig were benzoic acid and its conjugates. Minor metabolites were unchanged drug, amphetamine, norephedrine, an acid-labile precursor of benzyl methyl ketone and an unknown weakly acidic metabolite. The output of norephedrine was dose-dependent, being about 19% on the higher dose and about 1% on the lower dose. 5. Marked species differences in the metabolism of methamphetamine were observed. The main reaction in the rat was aromatic hydroxylation, in the guinea pig demethylation and deamination, whereas in man much of the drug, possibly one-half, was excreted unchanged.

scholarly journals The fate of benzoic acid in various species

1970 ◽  
Vol 118 (1) ◽  
pp. 47-51 ◽  
Author(s):  
J. W. Bridges ◽  
M. R. French ◽  
R. L. Smith ◽  
R. T. Williams
Keyword(s):  
Guinea Pig ◽  
Rhesus Monkey ◽  
Benzoic Acid ◽  
Urinary Excretion ◽  
Squirrel Monkey ◽  
Golden Hamster ◽  
Hippuric Acid ◽  
The Other ◽  
Main Metabolite ◽  
Fruit Bat

1. The urinary excretion of orally administered [14C]benzoic acid in man and 20 other species of animal was examined. 2. At a dose of 50mg/kg, benzoic acid was excreted by the rodents (rat, mouse, guinea pig, golden hamster, steppe lemming and gerbil), the rabbit, the cat and the capuchin monkey almost entirely as hippuric acid (95–100% of 24h excretion). 3. In man at a dose of 1mg/kg and the rhesus monkey at 20mg/kg benzoic acid was excreted entirely as hippuric acid. 4. At 50mg/kg benzoic acid was excreted as hippuric acid to the extent of about 80% of the 24h excretion in the squirrel monkey, pig, dog, ferret, hedgehog and pigeon, the other 20% being found as benzoyl glucuronide and benzoic acid, the latter possibly arising by decomposition of the former. 5. On increasing the dose of benzoic acid to 200mg/kg in the ferret, the proportion of benzoyl glucuronide excreted increased and that of hippuric acid decreased. This did not occur in the rabbit, which excreted 200mg/kg almost entirely as hippuric acid. It appears that the hedgehog and ferret are like the dog in respect to their metabolism of benzoic acid. 6. The Indian fruit bat produced only traces of hippuric acid and possibly has a defect in the glycine conjugation of benzoic acid. The main metabolite in this animal (dose 50mg/kg) was benzoyl glucuronide. 7. The chicken, side-necked turtle and gecko converted benzoic acid mainly into ornithuric acid, but all three species also excreted smaller amounts of hippuric acid.

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.

The Growth of Herpesvirus mulatto in Human Fibroblast

1974 ◽  
Vol 32 ◽  
pp. 244-245
Author(s):  
Glennelle Washington ◽  
Philip P. McGrath ◽  
Peter R. Graze ◽  
Ivor Royston
Keyword(s):  
Rhesus Monkey ◽  
Microscopic Study ◽  
Electron Microscopic Study ◽  
Peripheral Blood ◽  
Human Fibroblast ◽  
Rhesus Monkeys ◽  
Human Fibroblasts ◽  
Electron Microscopic ◽  
Specific Antisera ◽  
Peripheral Blood Leucocytes

Herpes-like viruses were isolated from rhesus monkey peripheral blood leucocytes when co-cultivated with WI-38 cells. The virus was originally designated rhesus leucocyte-associated herpesvirus (LAHV) and subsequently called Herpesvirus mulatta (HVM). The original isolations were from juvenile rhesus monkeys shown to be free of antibody to rhesus cytomegalic virus. The virus could only be propagated in human or simian fibroblasts. Use of specific antisera developed from HVM showed no relationship between this virus and other herpesviruses. An electron microscopic study was undertaken to determine the morphology of Herpesvirus mulatta (HVM) in infected human fibroblasts.

Application of an LC-MS/MS Method to a Urinary Excretion Study of Triflusal and its Main Metabolite 2-hydroxy-4-trifluoromethyl Benzoic Acid in Human Urine

2020 ◽  
Vol 16 (3) ◽  
pp. 328-334
Author(s):  
Jie Ge ◽  
Jin-Wen Wang ◽  
Qi-Yan Guo ◽  
Ai-Dong Wen
Keyword(s):  
Benzoic Acid ◽  
Urinary Excretion ◽  
Human Urine ◽  
Multiple Reaction Monitoring ◽  
Main Metabolite ◽  
Linear Relationships ◽  
Pharmacokinetic Properties ◽  
Liquid Chromatography Tandem Mass ◽  
Excretion Study ◽  
Acetate Aqueous Solution

Objective: A validated liquid chromatography-tandem mass spectrometry method (LCMS/ MS) was established to simultaneously determine the concentration of triflusal and its main metabolite 2-hydroxy-4-trifluoromethyl benzoic acid(HTB) in human urine. Methods: The separation was performed on a Dikma C18 column using isocratic elution with acetonitrile-4 mmol/L ammonium acetate aqueous solution containing 0.3 % formic acid water (78: 28, V/V). The method involved extraction with methanol using protein precipitation. The precursor-toproduct ion transitions with multiple reaction monitoring was m/z 247.1→161.1, 204.8→106.7and 136.9→93.0 for triflusal, HTB and salicylic acid(IS), respectively. The method showed good linear relationships over the ranges of 0.08 to 48 μg/mL and0.5 to 50 μg/mL. Results: It was the first time that a urinary excretion study of triflusal capsule as oral. The cumulative urinary recovery showed 8.5% and 2.7% for triflusal and HTB, respectively. Conclusion: This method was successfully used for evaluating the pharmacokinetic properties of triflusal and HTB in urine in Chinese healthy subjects.

scholarly journals Intratracheal inoculation of human varicella zoster virus (VZV; MAV strain) vaccine successfully induced VZV IgG antibodies in rhesus monkeys

2021 ◽  
Vol 37 (1) ◽  
Author(s):  
Jong-Min Kim ◽  
Chung-Gyu Park
Keyword(s):  
Rhesus Monkey ◽  
Varicella Zoster Virus ◽  
Humoral Immunity ◽  
Antibody Production ◽  
Rhesus Monkeys ◽  
Igg Antibodies ◽  
Simian Varicella Virus ◽  
Varicella Zoster ◽  
Varicella Virus ◽  
Strain Vaccine

Abstract Background The objective of this study was to investigate whether the use of live attenuated varicella zoster virus (VZV) MAV vaccination can efficiently induce VZV antibody production in naive rhesus monkeys as an approach to prevent simian varicella virus (SVV) reactivation in animals immunosuppressed for transplantation studies. Results Clinically available human VZV vaccine was used to induce the production of anti-VZV antibodies in rhesus monkeys. A vial of the vaccine was subcutaneously injected at 0 week, and the second and third vaccination was performed at 5 and 6 weeks by intratracheal inoculation. The titer of anti-VZV IgG was assessed at 0, 2, 4, 6, and 7 weeks. At 2 weeks, 3/16 were seropositive for VZV IgG. At 6 weeks, 9/16 were shown to be seropositive. At 7 weeks, 16/16 were found to be seropositive. Conclusions The VZV vaccine via intratrachael inoculation was shown to induce VZV IgG humoral immunity in rhesus monkeys and may be important immunosuppressed macaques for transplantation studies. Although the humoral immunity produced is an important finding, further studies will be necessary to confirm possible protection and it could protect probably against SVV infection in rhesus monkey.

scholarly journals Conjugated and unconjugated bilirubins in bile of humans and rhesus monkeys. Structure of adult human and rhesus-monkey bilirubins compared with dog bilirubins

1977 ◽  
Vol 167 (3) ◽  
pp. 535-548 ◽  
Author(s):  
S G Blumenthal ◽  
D B Taggart ◽  
R Ikeda ◽  
B H Ruebner ◽  
D E Bergstrom
Keyword(s):  
Chemical Composition ◽  
Gall Bladder ◽  
Rhesus Monkey ◽  
Rhesus Monkeys ◽  
Glucuronic Acid ◽  
Unknown Compound ◽  
Adult Human ◽  
Adult Humans ◽  
Technical Modifications ◽  
Working Day

1. Bilirubin-IXalpha, -IXalpha diglucuronide, -IXalpha monoglucuronide, -IXalpha monoglucoside -IXalpha monoxyloside, a bilirubin-IXalpha diconjugate containing glucose and another unknown compound, and bilirubin-IXbeta are present in gall-bladder bile of adult human, rhesus monkey and dog. Dog bile normally also contains other bilirubin-IXalpha diconjugates, i.e. compounds containing two conjugating sugars such as glucuronic acid and glucose, glucuronic acid and xylose and glucose xylose. 2. Azopigments alphaF, alphaO, alpha2, alpha3, betax and delta derived from human and rhesus-monkey bilirubins are identical in their chemical composition with those obtained from the dog. 3. Azopigments alphaF and betax found in diazotized biles of adult humans, rhesus monkeys and dogs are products of unconjugated bilirubin-IXbeta. 4. Technical modifications of previously published procedures [Heirwegh, Fevery, Michiels, Van Hees & Compernolle, (1975) Biochem. J. 145, 185-199] were introduced which make it possible to separate the bilirubins, diazotize the separated bilirubins, extract the azopigments and chromatograph them in one working day (6-8h).

THE BI-DIRECTIONAL PLACENTAL TRANSFER OF I131 3:5:3' TRIIODOTHYRONINE IN THE RHESUS MONKEY

PEDIATRICS ◽  
1965 ◽  
Vol 35 (5) ◽  
pp. 743-752
Author(s):  
Marvin A. Schultz ◽  
Jean B. Forsander ◽  
Ronald A. Chez ◽  
Donald L. Hutchinson
Keyword(s):  
Rhesus Monkey ◽  
Thyroid Hormones ◽  
Concentration Gradient ◽  
Rhesus Monkeys ◽  
Placental Transfer ◽  
Reverse Direction ◽  
Maternal Transfer ◽  
Maternal Circulation ◽  
Unknown Compound ◽  
Maternal Thyroid

The placental transfer of I131-labeled triiodothyronine has been studied in Rhesus monkeys. The majority of maternal to fetal placental transfer of radioactivity was in the form of iodide and a chemically unrecognized compound on chromatograms. Only traces of triiodothyronine or thyroxine were detected. In the fetal to maternal transfer studies, triiodothyronine was more readily transferred into the maternal circulation with small amounts of iodide and a similar unknown compound appearing. This substance may be sulfate conjugated triiodothyronine. There was a considerably higher concentration gradient used in the fetal to maternal transfers than in the reverse direction. The implications of this gradient difference are discussed. The data from this study add further evidence to the clinical experience that maternal thyroid hormones are not readily available to meet all of the fetal needs during the latter part of pregnancy.

A safe and fast-acting surgical anesthetic for use in the guinea pig

1975 ◽  
Vol 38 (3) ◽  
pp. 538-539 ◽  
Author(s):  
D. W. Shucard ◽  
M. Andrew ◽  
C. Beauford
Keyword(s):  
Guinea Pig ◽  
Guinea Pigs ◽  
Intramuscular Injection ◽  
Methyl Ketone ◽  
Ketamine Hydrochloride ◽  
Fast Acting

Ketamine [dl-2-(o-chlorophenyl)-2-(methylamino)cyclohexanone] hydrochloride was used in conjunction with Acepromazine [10–3-(dimethylamino)-propyl]phenothiazin-2-yl-methyl ketone] Maleate to produce surgical depth anesthesia in guinea pigs. In tests with 97 animals, an intramuscular injection of 44 mg/kg ketamine hydrochloride plus 2 mg Acepromazine Maleate was found to be effective in producing a surgical level of anesthesia within 2 min after administration. The anesthetic state lasted for an average of 1.5 h and could be safely extended by supplemental administrations of the drugs. This anesthetic combination was found to be fast acting, safe, and easily controlled.

Sign in / Sign up

Export Citation Format

Share Document