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1. |
Introduction |
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Journal of Toxicology and Environmental Health,
Volume 2,
Issue 4,
1977,
Page 3-3
Jerry Brunton,
Lloyd Davis,
William Huber,
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ISSN:0098-4108
DOI:10.1080/15287397709529473
出版商:Taylor & Francis Group
年代:1977
数据来源: Taylor
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2. |
Participants |
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Journal of Toxicology and Environmental Health,
Volume 2,
Issue 4,
1977,
Page 4-4
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ISSN:0098-4108
DOI:10.1080/15287397709529474
出版商:Taylor & Francis Group
年代:1977
数据来源: Taylor
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3. |
Food and drug administration statement of problem |
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Journal of Toxicology and Environmental Health,
Volume 2,
Issue 4,
1977,
Page 727-730
MarylnK. Perez,
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ISSN:0098-4108
DOI:10.1080/15287397709529475
出版商:Taylor & Francis Group
年代:1977
数据来源: Taylor
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4. |
Industry statement of problem |
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Journal of Toxicology and Environmental Health,
Volume 2,
Issue 4,
1977,
Page 731-733
HelenH. Birkhead,
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ISSN:0098-4108
DOI:10.1080/15287397709529476
出版商:Taylor & Francis Group
年代:1977
数据来源: Taylor
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5. |
Pharmacokinetic prediction of tissue residues |
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Journal of Toxicology and Environmental Health,
Volume 2,
Issue 4,
1977,
Page 735-756
LewisW. Dittert,
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摘要:
The applications of pharmacokinetic modeling to the prediction of tissue residues of drugs in food‐producing animals are reviewed. The properties of the one‐compartment open model are discussed, and the application of this model to the serum levels, urine outputs, and tissue residues of sulfamethazine and its metabolites in sheep is described. The properties of the two‐compartment model are discussed, and the application of this model to the serum levels and urine outputs of dicloxacillin in humans is described. Complexities encountered with drugs such as pentobarbital, the tetracyclines, etidronate, and salicylate are discussed as examples of pharmacokinetic behavior that make both modeling and tissue residue prediction difficult.
ISSN:0098-4108
DOI:10.1080/15287397709529477
出版商:Taylor & Francis Group
年代:1977
数据来源: Taylor
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6. |
Stable and short‐lived isotopes in the study of tissue distribution |
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Journal of Toxicology and Environmental Health,
Volume 2,
Issue 4,
1977,
Page 757-785
GeorgeA. Digenis,
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摘要:
Two relatively novel techniques that are utilized in the study of tissue distribution of drugs are discussed. The first technique, GC‐MS fragmentography, provides an opportunity for the identification and quantification of several compounds and internal standards, in the same analysis, at picogram to nanogram amounts. The second technique utilizes short‐lived radioisotopes and external scintigraphy. This approach can continuously monitor the tissue and organ distribution of an appropriately labeled compound. It produces quantifiable results and provides an opportunity for doing several experiments on the same animal in a noninvasive manner.
ISSN:0098-4108
DOI:10.1080/15287397709529478
出版商:Taylor & Francis Group
年代:1977
数据来源: Taylor
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7. |
Application of pharmacokinetic methods to the drug residue profile |
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Journal of Toxicology and Environmental Health,
Volume 2,
Issue 4,
1977,
Page 787-801
H. D. Mercer,
J. D. Baggot,
R. A. Sams,
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摘要:
A pharmacokinetic approach to the delineation of a drug residue profile in food‐producing animals has been presented. It is recognized that the determination of a drug withdrawal period is one of the costly developmental procedures in drug development for food animals; thus it is believed that in the early developmental phases, a thorough pharmacokinetic characterization of a drug in the target species would greatly facilitate the design and quality of studies conducted in the later phases of new drug development. It is suggested that drugs that are intended for use in food animals can be characterized kinetically in less costly studies, the results of which might be used to determine the feasibility of developing a drug that might cause serious residue problems. It is also suggested that the pharmacokinetic modeling of a drug in the target animal may provide an essential data base for calculating dosage rates and intervals that directly relate to the efficacy aspects of drug development.
ISSN:0098-4108
DOI:10.1080/15287397709529479
出版商:Taylor & Francis Group
年代:1977
数据来源: Taylor
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8. |
Non‐drug‐related residues in tracer studies |
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Journal of Toxicology and Environmental Health,
Volume 2,
Issue 4,
1977,
Page 803-814
Charles Rosenblum,
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摘要:
Factors involved in residue studies with radioactive tracers are discussed. Three types of metabolic management of14C‐labeled compounds are described. Intact incorporation into protein of chick muscle is demonstrated with L‐O‐ethyl‐[14C/threonine. Retention of unchanged and quantitatively recoverable parent compound occurred with [14C] thiabendazole sprayed on oranges. The latter drug fed to animals was retained in tissue partly intact, but mostly metabolized to recognizable detoxification products, and ultimately to endogenous tissue components. The latter type of residue was termed a “nonmetabolite” residue. The extreme case of extensive metabolism to products structurally unrelated to the parent compound was illustrated with [14C] ronidazole administered to turkeys.
ISSN:0098-4108
DOI:10.1080/15287397709529480
出版商:Taylor & Francis Group
年代:1977
数据来源: Taylor
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9. |
Experiences in dealing with drug‐related bound residues |
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Journal of Toxicology and Environmental Health,
Volume 2,
Issue 4,
1977,
Page 815-826
PremS. Jaglan,
M. Weldon Glenn,
A. William Neff,
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摘要:
Although more than 90% of the radioactivity was excreted in the urine and feces within 10 days of oral treatment of sheep with a single dose of p [14C]toluoyl chloride phenylhydrazone (TCPH), persistent blood residues (5–6 ppm) were observed for at least 21 days. The14C residues were largely localized in erythrocytes and covalently bound to both heme and globin. Only the phenyl group of the phenylhydrazlne part of TCPH was present as14C bound residues. An analytical procedure to measure the level of phenyl groups incorporated in heme, based on their oxidation to benzoic acid, was developed to monitor residues in treated animals. Relay metabolism in rats was studied by feeding sheep blood containing14C residues form [14C] TCPH treatment. No retention of14C residues in rat tissues was observed, which contrasted with the TCPH metabolism. A 90‐day relay toxicity study in rats, which were fed dried blood from treated sheep containing up to 2,000 times the potential exposure to residues in the human diet, indicated no observable toxic responses. It is concluded that these data support a tolerance of 6 ppm TCPH equivalents in blood.
ISSN:0098-4108
DOI:10.1080/15287397709529481
出版商:Taylor & Francis Group
年代:1977
数据来源: Taylor
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10. |
Methodology for the determination of bioavailability of labeled residues |
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Journal of Toxicology and Environmental Health,
Volume 2,
Issue 4,
1977,
Page 827-845
HugoE. Gallo‐Torres,
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摘要:
Methods are described for the determination of bioavailability of lipo‐ and hydro‐soluble compounds in the rat. These procedures involve catheterization of the portal vein and/or intestinal lymphatics to study absorption in unanesthetized animals. Catheterization of the common bile duct prevents recycling of materials through the entero‐porto‐hepato‐biliary circulation (EPHBC). Steady‐state conditions are ensured by constant infusion of bile or a solution of bile acids into the stomach or duodenum. The techniques and physiological considerations discussed in detail here have resulted in new proposed animal preparations, of value in the accurate determination of the bioavailability of labeled residues ingested by the second species. Since intake must be adequate to permit meaningful conclusions, the concentration of radioactivity in the harvested homogenized tissue is increased by lyophilization. The lyophilized material is compressed into pellets of adequate size. The animals, kept in restraining cages to prevent coprophagy, are allowed to eat the labeled residue spontaneously, if necessary, for 48 and even 12 hr. Bile, urine, and feces are collected for a sufficient length of time to allow quantitative excretion of the labeled residue, if no absorption takes place. Co/lection of these excreta must be complete. It is essential to account for most—if not all—of the radioactivity administered. Data so obtained allow an accurate balance between intake and excretion of the labeled residue. The presence of radioactivity in the intestinal wall, carcass, liver, and urine is indicative of absorption. The appearnace of radioactivity in the bile also indicates absorption, in addition to suggesting that the compound(s) may undergo EPHBC. The extent of recovery of the administered radioactivity in the luminal contents and feces indicates the extent to which the labeled residue is not bioavailable. Evaluation of data obtained with these new animal models should permit corresponding upward adjustments of the minimum levels of residues allowable in the tissue of animals intended for human consumption.
ISSN:0098-4108
DOI:10.1080/15287397709529482
出版商:Taylor & Francis Group
年代:1977
数据来源: Taylor
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