摘要:

1. Oral doses of [14C]Ionox 312 were not appreciably absorbed by rats.2. Urine, exhaled air, fatty tissues and carcasses contained only 0.01.0.1% of the administered radioactivity.3. Negligible amounts of radioactivity (>0.001%) were excreted in the bile.

ISSN:0049-8254    

DOI:10.3109/00498257209036229

出版商:Taylor&Francis    

年代:1972

数据来源: Taylor

摘要:

1. The ability of rats to degrade [14C]Ionox 330 in the alimentary canal was not altered by prior feeding of the compound.2. [14C]Ionox 330 was not absorbed from the alimentary canal of pretreated animals.3. A small quantity of Ionox 330 was oxidized within the alimentary canal followed by a limited absorption of the products.4. The oxidation of Ionox 330 within the gut and the absorption of products were independent of dose level (20 and 400 mg/kg body weight).5. It is unlikely that an enzymic mechanism is involved in the initial stage of oxidation of Ionox 330in vivo

ISSN:0049-8254    

DOI:10.3109/00498257209036230

出版商:Taylor&Francis    

年代:1972

数据来源: Taylor

摘要:

1. [14C]Phenol has been administered to man (dose, 0.01 mg/kg) and 18 animal species (25 mg/kg) and the urine examined for metabolites by radiochromatogram scanning.2. In three men 90% of an oral dose was excreted in 24 h mainly as phenylsulphate (77% of 24 h excretion) and phenylglucuronide (16%) with very small amounts of quinol sulphate and glucuronide.3. Four metabolites, the sulphates and glucuronides of phenol and quinol, were found in the urine of the rodents, the rat, mouse, jerboa, gerbil, hamster, lemming and guinea-pig after an oral dose of phenol.4. Three metabolites were excreted by some species, namely, phenol and quinol glucuronides and phenylsulphate by the squirrel monkey and capuchin monkey, and phenol and quinol sulphates and phenylglucuronide by the ferret, dog, hedgehog and rabbit.5. Two metabolites were excreted by the rhesus monkey, fruit bat and hen (phenylsulphate and phenylglucuronide) and by the cat (phenylsulphate and quinol sulphate). One metabolite (phenylglucuronide) only was excreted by the pig.6. The cat appeared to form no phenylglucuronide and the pig no phenylsulphate, but detailed examination of radiochromatograms showed that the cat did excrete small amounts of the glucuronide and the pig excreted small amounts of the sulphate.7.In vitrostudies with rat and pig liver preparations showed that the rat preparations conjugate phenol with sulphate and glucuronic acid with roughly equal facility, but the pig liver preparations conjugated phenol with glucuronic acid at a much faster rate than with sulphate.

ISSN:0049-8254    

DOI:10.3109/00498257209036231

出版商:Taylor&Francis    

年代:1972

数据来源: Taylor

摘要:

1. Sensitive methods were developed for identification of the antihypertensive agent guanoxan (2-guanidinomethyl-1,4-benzodioxan) and some possible metabolites, and for the quantitative determination of guanoxan and 6- or 7-hydroxyguanoxan extracted from biological media.2. Urine from a number of hypertensive patients and from a normal human subject receiving oral guanoxan (20 to 200 mg daily) contained non-conjugated 6- or 7-hydroxyguanoxan in amounts ranging from 11.7% to over 50% of the daily amount taken. This represented the main mode of clearance of the drug.3. Faeces from these patients and the normal human subject contained only low levels of both guanoxan and 6- or 7-hydroxyguanoxan.4. No metabolite of guanoxan other than 6- or 7-hydroxyguanoxan and no conjugate of either compound was detected in human excreta.5. Following oral administration, guanoxan was rapidly and extensively absorbed and subject to aromatic hydroxylation in man.

ISSN:0049-8254    

DOI:10.3109/00498257209036232

出版商:Taylor&Francis    

年代:1972

数据来源: Taylor

摘要:

1. 3-Acetamido-6-methyl-8-n-propyl-s-[3-14C]triazolo [4,3-a]pyrazine ([14C] I.C.I. 58,301) an antibronchoconstrictor has been prepared and its distribution and metabolism studied in six animal species.2. The compound was well absorbed after oral administration, extensively metabolized, widely distributed in the body and rapidly excreted in urine. In small animals>0.5% of the administered radioactivity could be detected in exhaled air.3. Maximum tissue levels in the guinea pig occurred 1 1/2-2h after an oral dose. Labelled material could be detected in the lung and serum of the guinea pig 5 min after an oral dose (5 mg/kg).4. Six metabolites were identified and together with I.C.I. 58,301 these constituted 90% of the14C-labelled material in the urine from a rhesus monkey. The principal metabolic pathways involvedN-deacetylation and hydroxylation of the alkyl side chains;N-methylation in the heterocyclic ring was also observed.5. Two of the major metabolites have been shown to be biologically less active than I.C.I. 58,301.6. Interspecies differences in metabolism appear to be quantitive rather than qualitative.

ISSN:0049-8254    

DOI:10.3109/00498257209036233

出版商:Taylor&Francis    

年代:1972

数据来源: Taylor

摘要:

1. When [14C]1-diethylcarbamyl-4-methylpiperazine was orally administered to rats, 97% of the radioactivity was excreted in the 24 h urine. Unchanged drug excreted in the urine accounted for about 15% of the dose.2. Two major metabolites present in the urine have been identified as 1-ethylcarbamyl-4-methylpiperazine (about 23% dose) and as 1-diethylcarbamyl-4-methylpiperazine-4-oxide (about 50% dose).

ISSN:0049-8254    

DOI:10.3109/00498257209036234

出版商:Taylor&Francis    

年代:1972

数据来源: Taylor

摘要:

1. The urinary metabolites of 4,6-dimethoxy-2-sulphanilamidopyrimidine (sulphadimethoxypyrimidine), have been examined in man, the rhesus monkey, rabbit and rat.2. The orally administered drug is slowly excreted in man and rat (10% or less in 24 h) but relatively rapidly in the monkey and rabbit (60% or more in 24 h).3. In man and the rhesus monkey, a major urinary metabolite of the drug was found to be itsN1-glucuronide. None of this glucuronide was found in rabbit urine and only minor amounts in rat urine.4. Of nine sulphanilamidopyrimidines examined, only three formN1-glucuronides in man and monkey but not in other species. This finding is discussed.

ISSN:0049-8254    

DOI:10.3109/00498257209036235

出版商:Taylor&Francis    

年代:1972

数据来源: Taylor

摘要:

1. Following the intravenous administration of [4-14C]mestranol (34μg/kg) to female rats, 44.9 and 3.3% of the dose of radioactivity was excreted in the faeces and urine, respectively, in 3 days. Similarly, after administration of [4-14C]estradiol (26μg/kg) 63% was excreted in the faeces and 11% was excreted in the urine in 3 days. Excretion of both compounds declined to 1% dose on the 5th day.2. A considerable portion (up to 50%) of the radioactivity eliminated in urine and faeces could not be hydrolyzed withβ-glucuronidase or by solvolysis. A possible conjugation of metabolites with compounds having SH-groups is discussed.3. The amount of radioactivity found in brain and adrenals 4 h after injection of [14C]mestranol was 2-3 times greater than found after injection of [14C]estradiol. Following administration of [14C]mestranol extracts of body fat and brain contained mestranol as the main radioactive component.4. The whole-body radioactivity in mice after administration of [14C]mestranol was determined. The radioactivity extractable by a mixture of methylene dichloride-ethanol, nearly 40% dose at 2 h after dosage, fell to 1.4% dose at 48 h; the radioactivity not extractable with these solvents,<50% dose at 2 h after dosage, fell to a plateau of 15% dose at 48 h. Most of this non-extractable radioactivity was insoluble in water, and also in ether after acid hydrolysis.5. After administration of [14C]mestranol to a female rat, only 2.5% of the radioactivity was expired as14CO2within 4 days indicating no significant degradation of the steroid nucleus.6. Some metabolites of mestranol were separated from faecal extracts by column chromatography on alumina. After administration of [3-methyl-3H, 4-14C]mestranol some metabolites (peaks I, III, VI) have an unaltered 3-methoxy group, while others (II, IV, V) are demethylated to derivatives of ethynylestradiol.

ISSN:0049-8254    

DOI:10.3109/00498257209036236

出版商:Taylor&Francis    

年代:1972

数据来源: Taylor

摘要:

1. Tricyclic antidepressant drugs bind to cytochrome P-450 with very high affinities and are useful tools for studying ligand interaction with cytochrome P-450 in different microsomal preparations. The effects of three days treatment of rats with phenobarbital and 3,4-benzpyrene on the microsomal binding and hydroxylation of two such drugs nortriptyline (NT) and desmethylimipramine (DMI) are described.2. Treatment with 3,4-benzpyrene slightly increased the rate of hydroxylation of NT and DMI, whereas repeated administration of phenobarbital reduced the same rates.3. In microsomes from untreated and 3,4-benzpyrene-treated animals these drugs elicited a type I spectral change, but in microsomes from phenobarbitaltreated animals a type II spectral change was obtained. It was not possible to obtain a type II spectral change with NT or DMI in control microsomes upon addition of phenobarbitalin vitro4. Thus, it seems that phenobarbital treatment, by affecting cytochrome P-450 or its microenvironment, causes a qualitative change in the ligand interaction between the cytochrome and NT and DMI. This may explain the slightly decreased rates of hydroxylation of these drugs observed with microsomes from phenobarbital-treated rats.

ISSN:0049-8254    

DOI:10.3109/00498257209036237

出版商:Taylor&Francis    

年代:1972

数据来源: Taylor