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  • Rat  (123)
  • pharmacokinetics  (48)
  • Springer  (171)
  • Copernicus
  • 1970-1974  (171)
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  • Springer  (171)
  • Copernicus
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  • 1
    Electronic Resource
    Electronic Resource
    Springer
    Calcified tissue international 10 (1972), S. 238-251 
    ISSN: 1432-0827
    Keywords: Growth ; Bone ; Rat ; Tetracycline
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Description / Table of Contents: Résumé La vitesse de croissance normale en longueur de la métaphyse proximale du tibia est déterminée chez le rat Sprague-Dawley entre les âges de 20 et 100 jours, en utilisant la méthode à la tétracycline. Le taux de croissance ne varie que légèrement dans les groupes d'âges différents. Il est plus élevé chez les animaux jeunes et décroit considérablement en fonction de l'augmentation de l'âge. Les rats mâles présentent une croissance plus élevée que les femelles. Cette étude a pour but de mettre au point une méthode permettant de déterminer les facteurs expérimentaux, liés à la croissance en longueur du rat.
    Abstract: Zusammenfassung Die normale Längenwachstums-Geschwindigkeit der proximalen Wachstumsplatte der Tibia wurde bei Sprague-Dawley-Ratten in einem Alter zwischen 20 und 100 Tagen mittels der Tetracyclinmethode gemessen. Die Wachstumsgeschwindigkeit variierte nur wenig innerhalb der einzelnen Altersgruppen. Die Geschwindigkeit war bei jungen Tieren am höchsten und nahm mit zunehmendem Alter beträchtlich ab. Männliche Ratten wuchsen schneller als weibliche. Diese Arbeit dient als Grundlage, um die experimentelle Beeinflussung des Längenwachstums der Ratte abschätzen zu können.
    Notes: Abstract The rate of normal growth in length from the proximal growth plate of the tibia in the Sprague-Dawley rat was measured between 20 and 100 days of age using the tetracycline method. The growth rate varied only slightly within different age groups. The rate was highest in young animals and decreased considerably with increasing age. Male rats grew faster than female. This study is intended to provide a base for an evaluation of experimental influence on the growth in length of the rat.
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    Calcified tissue international 14 (1974), S. 283-289 
    ISSN: 1432-0827
    Keywords: Sodium fluoride ; Osteoporosis ; Bone ; Strength ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Description / Table of Contents: Résumé L'utilisation thérapeutique de fluorure de sodium a été recommandée dans le traitement de diverses maladies osseuses ostéopéniques. Cet emploi est basé principalement sur les effects ostéosclérotiques bien connus du fluorure de sodium, mais on connait mal son effet sur la force de résistance osseuse. L'influence de diverses concentrations de fluorure de sodium sur la force de résistance osseuse de jeunes rats soumis à des régimes riches et pauvres en calcium a été étudiée. L'administration de fluorure de sodium augmente le diamètre osseux, indiquant une stimulation de la formation de l'os périosté, mais la force de résistance osseuse est réduite ou non modifiée par l'ingestion de fluor.
    Abstract: Zusammenfassung Die therapeutische Verwendung von Natriumfluorid ist für eine Anzahl von Knochenmangel-Krankheiten empfohlen worden. Die Empfehlungen basieren hauptsächlich auf den bekannten osteosklerotischen Wirkungen von Natriumfluorid; über dessen Effekt auf die Knochenstärke ist wenig bekannt. In dieser Arbeit wurde der Einfluß verschiedener Konzentrationen von Natriumfluorid auf die Knochenstärken von wachsenden Ratten mit hoher und niederer Calciumeinnahme untersucht. Die Verabreichung von Natriumfluorid erhöhte den Knochendurchmesser, was auf eine Stimulierung der Periostbildung hinwies, die Knochenstärke wurde jedoch durch Fluorideinnahme herabgesetzt oder nicht beeinflußt.
    Notes: Abstract The therapeutic use of sodium fluoride has been recommended in a variety of osteopenic bone diseases. The recommendations are based mainly on the known osteosclerotic effects of sodium fluoride and little information is available as to its effect on bone strength. The influence of various concentrations of sodium fluoride on bone strength in growing rats on high and low calcium diets was studied. The administration of sodium fluoride increased bone diameter, indicating stimulation of periosteal bone formation, but bone strength was reduced or not affected by fluoride ingestion.
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    Calcified tissue international 13 (1973), S. 113-129 
    ISSN: 1432-0827
    Keywords: Kinetics ; Growth ; Epiphyses ; Hypophysectomy ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Description / Table of Contents: Résumé La largeur de la métaphyse tibiale, la zone indifférenciée, la zone sériée et les cellules en dégénerescence ont été observées chez des rats Sprague-Dawley normaux et hypophysectomisés. La production cellulaire de la métaphyse est déterminée sur la base de la croissance osseuse longitudinale déterminée par l'oxytétracycline et la taille des cellules en dégénérescence. La diminution de la croissance osseuse longitudinale, en fonction de l'augmentation de l'âge et après hypophysectomie, est due partiellement, à la diminution de production cellulaire et partiellement à une décroissance de la taille des cellules en dégénérescence dans la métaphyse. L'influence de la production cellulaire et de l'activité mitotique prédomine.
    Abstract: Zusammenfassung Die Breite der proximalen Wachstumsplatte der Tibia, deren undifferenzierter und säulenförmiger Zone und die Größe der nahe bei der Metaphyse auftretenden degenerativen Zellen wurden in normalen und hypophysektomierten Sprague-Dawley-Ratten bestimmt. Die Zellproduktion in der Wachstumsplatte wurde aus dem longitudinalen Knochenwachstum berechnet, welches mittels Oxytetracyclin und der Größe der degenerativen Zellen bestimmt wurde. Es wurde festgestellt, daß die Abnahme des longitudinalen Knochenwachstums bei zunehmendem Alter und nach Hypophysektomie zum Teil einem Rückgang in der Zellproduktion, zum Teil einer Verminderung der Größe der degenerativen Zellen in der Wachstumsplatte zuzuschreiben ist. Der Einfluß der Zellproduktion, und somit der mitotischen Aktivität, herrscht vor.
    Notes: Abstract The width of the proximal growth plate of the tibia, its undifferentiated and columnar zone and the size of the degenerative cell close to the metaphysis, were determined in normal and hypophysectomized Sprague-Dawley rats. The cell production in the growth plate was calculated from the longitudinal bone growth determined with oxytetracycline and the degenerative cell size. It was found that the decrease in longitudinal bone growth with increasing age and after hypophysectomy, is due partly to a decrease in cell production, and partly to a decrease in degenerative cell size in the growth plate. The influence of cell production and thus the mitotic activity predominates.
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  • 4
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 5 (1972), S. 44-52 
    ISSN: 1432-1041
    Keywords: alprenolol ; serum drug level ; exercise ; man ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The effects of alprenolol on heart rate and systolic blood pressure were studied in healthy subjects during standardized exercise on a bicycle ergometer. In one series of experiments, in which serum concentrations of alprenolol were also measured, the effects of single oral doses of 50, 100 and 200 mg of alprenolol and a placebo were compared by a double blind cross-over technique. In a second series of experiments 100 mg alprenolol was given four times in one day and the effect was followed for up to eighteen hours after the last dose. — Alprenolol diminished the expected increase in heart rate and systolic blood pressure during exercise. The reduction of exercise tachycardia in a given individual was linearly related to the logarithm of the dose or the serum concentration of alprenolol. The serum concentrations required for a given reduction of exercise tachycardia varied almost one hundred-fold amongst the subjects studied. The biological availability of alprenolol was dose-dependent, probably due to a limited capacity biotransformation of the drug before it entered the general circulation. After a single dose the serum level of alprenolol and its chronotropic effect diminished at a rate corresponding to an elimination half life of about two hours. This rate of elimination was consistent with that calculated from the results of the four dose study.
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  • 5
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 5 (1973), S. 174-180 
    ISSN: 1432-1041
    Keywords: Tricyclic antidepressant ; nortriptyline ; metabolism ; urine ; pharmacokinetics ; twins ; man
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The urinary excretion of nortriptyline (NT) and five of its metabolites was studied by quantitative gas chromatography in 22 twins and 7 unrelated healthy subjects after single (1 mg/kg) and multiple oral doses (0.4 mg/kg t.i.d.) of NT hydrochloride. A mean recovery of 62% of the dose was found after both single and multiple doses. The metabolite pattern in the urine was qualitatively and quantitatively identical in the two regimes, but there were marked variations in the pattern of metabolites between individuals. The disappearance rate of NT from the plasma was mainly determined by the metabolism of NT to 10-hydroxynortriptyline, which varied considerably between individuals. The data suggest that in certain rapid NT metabolizers, the upper limit for the overall clearance of NT from the plasma (if extrahepatic metabolism is assumed to be negligible) might be set by the blood flow through the liver.
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  • 6
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 6 (1973), S. 268-270 
    ISSN: 1432-1041
    Keywords: Diphenhydramine ; orphenadrine ; gas-liquid chromatography ; N-selective detector ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary A method is described for the assay of nanogram quantities of diphenhydramine and orphenadrine in human plasma. The procedure employs gas-liquid chromatography and a high sensitivity nitrogen detector. It has been used to assay diphenhydramine in plasma after oral administration of therapeutic doses.
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  • 7
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 6 (1973), S. 234-238 
    ISSN: 1432-1041
    Keywords: Phenobarbital ; neonate ; maternal-fetal exchange ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Plasma concentrations of phenobarbital were measured in 18 newborn infants for one to two weeks after birth. The drug had been administered prenatally to the mothers as part of treatment for maternal hypertension or toxaemia. The plasma half-life of the drug in the infants (77–404 h) was inversely correlated with the extent of prenatal exposure to it. In three infants a bi-phasic plasma curve was found as there was a sudden change from slow to fast disappearance on the 5th to 7th day of life.
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  • 8
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 7 (1974), S. 407-414 
    ISSN: 1432-1041
    Keywords: Diuretic ; indapamide ; human pharmacology ; toxicology ; pharmacokinetics ; TLC assay
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacology, toxicology and kinetics of a new diuretic indapamide, have been studied in six normal volunteers following a single oral dose of 40 mg. Pronounced diuresis was found, commencing three hours after ingestion, with a peak urinary flow at four to six hours, and continuing for a total of thirty-six hours. A fall in systolic standing blood pressure occurred twenty four hours after ingestion, coincident with the period of maximum dehydration. Free water clearance rose, accompanied by increased urinary losses of Na+, K+ and Cl− and alkalinisation of the urine comparable to the actions of benzothiadiazines. Total urinary losses of Ca2+, Mg2+ and PO 4 3− rose in spite of a fall in urinary concentrations of these ions. The Ca2+ effect compares with the acute ionic effects of other diuretics. No renal, hepatic or haematological toxic effect was demonstrated. The blood sugar level was not disturbed. Serum uric acid rose to abnormal levels although the change did not reach statistical significance. — A thin layer chromatographic method, with a sensitivity limit of 0.1 µg/ml., has been developed for the assay of indapamide in urine. The urinary excretion rates of the volunteers measured over forty-eight hours indicate that the drug is rapidly absorbed with a peak excretion, 2.9±1.3 µg/min occurring three hours after ingestion. The drug is eliminated bi-phasically with an initial short rapid elimination followed by a slower exponential decline with a mean elimination half-life of 10.3 ± 3.9 h. The mean urinary excretion of unchanged indapamide over forty-eight hours was 4.4±1.4% of the administered dose. — It is concluded that indapamide is an effective long-acting diuretic with comparable action to the benzothiadiazine diuretics, but without an effect on blood sugar level in single doses in normal subjects. In contrast with other diuretics, indapamide appears to be extensively metabolised in man, and its longer duration of action to be related to a longer elimination half-life.
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  • 9
    ISSN: 1432-1041
    Keywords: Oral antidiabetic drug ; butylbiguanide ; pharmacokinetics ; two-compartment open model ; plasma concentration ; liver concentration ; intestine concentration ; man
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary 50 mg14C-Butylbiguanide was administered intravenously to 4 diabetic patients and 100 mg14C-butylbiguanide orally to 5 further diabetics. The concentrations of the drug in plasma, intestinal fluid, intestinal epithelium and liver tissue were determined and the renal excretion of the biguanide measured. Irregularities in the plasma concentration curve were observed which appeared as systematic deviations from the ideal curve of a biexponential function. Because these deviations occurred only in the middle phase of the plasma concentration curve, it was nevertheless possible to calculate the pharmacokinetic parameters of butylbiguanide by use of a two-compartment open model. The principal pharmacokinetic parameters were determined according to this model after intravenous dosing and the following mean values were obtained:t 1/2 (β)=4.6 h (β=0.15 h−1),C P 0 =0.85µg/ml,V D =218 l,V T =157 l,V P =62 l,k 12=0.69 h−1,k 21=0.44 h−1,k el =0.54 h−1. Within 48 h after administration, an average of 72.4% of the intravenous and 74.4% of the oral dose had been excreted in the urine. Total clearance (Cl tot) averaged 536 ml/min and renal clearance (Cl ren) 393 ml/min. High concentrations of butylbiguanide were observed in the intestinal fluid (100–700 mg/ml) 20–40 min after oral administration. It was found that the drug accumulates in intestinal fluid, intestinal epithelium and liver tissue, and that it is secreted into the intestinal lumen. The concentrations of butylbiguanide in intestinal and liver tissue were 10–46 times higher than in plasma. The secretion of biguanide into the intestinal lumen may occur via the bile or the intestinal mucosa, but there is no evidence of significant biliary excretion of butylbiguanide.
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  • 10
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 7 (1974), S. 295-305 
    ISSN: 1432-1041
    Keywords: Mestranol ; ethynyloestradiol ; contraceptive compounds ; demethylation ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The oestrogenic activity of mestranol depends on its demethylation to ethynyloestradiol. The reaction has been studied in man. The compound disappeared exponentially from plasma during the first 4 h after i.v. injection of [4-14C-] mestranol. The “metabolic clearance” for this phase amounted to 31.8 1/day per kg body weight. Methoxy-3H-labelled mestranol was prepared for the further studies, because if it is demethylated, the tritium would be transferred to HTO, which would equilibrate immediately with body water. The appearance in body water of tritium from [methoxy-3H-] mestranol could be described by two exponential functions, which corresponded to bi-phasic disappearance of the original compound from plasma. The rate constant of the first stage was: γ1=0.835 h−1, and of the second: γ2=0.034 h−1. HTO radioactivity was eliminated from the body by exchange of water. From the data obtained, a three-compartment model was constructed of the transfer of tritium from [methoxy-3H-] mestranolinto body water, which permitted computer simulation of the partial processes. The compartmental analysis suggested that mestranol differed from ethynyloestradiol mainly in the delayed and protracted manner in which hormonally active oestrogen entered the circulation. The proportion of [methoxy-3H-] mestranol demethylated to ethynyloestradiol (demethylation ratio) varied little, 53.7±5.0% (x±SD; n=6), and was consistent with clinical observations that mestranol is half as potent an oestrogen as ethynyloestradiol. Thus, the dose of mestranol required to produce a given effect has to be twice as large as that of ethynyloestradiol.
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