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  • 1
    ISSN: 1573-8744
    Keywords: rate of absorption ; rate of renal reabsorption ; extraction theory ; partition coefficientin vivo ; pH of lumenal contents
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Equations have been derived which quantitatively describe the rate of gastrointestinal and buccal absorption of acidic and basic drugs as a function of pH of aqueous lumenal contents and time. The equations have been used to fit observed data in the literature, and the estimated parameters are reported. An equation which describes the renal clearance of an acidic or basic drug as a function of urinary pH is also derived. In essence, the equations quantitate the pH-partition hypothesis and explain most, if not all, related observed data in the literature. The results suggest that the aqueous diffusion layer may not rate-limit absorption of monomeric drug molecules but that absorption is rate-limited by transfer of drug out of the membrane in vivo.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1573-8744
    Keywords: cancer chemotherapy ; ARA-C (cytosine arabinoside) ; L1210 mouse leukemia ; mathematical predictions
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract The results of clinical treatment of the L1210 mouse leukemia with cytosine arabinoside have been modeled with a direct action exponential growth model. Experimental growth kinetic and pharmacokinetic data were used to evaluate portions of the model. The data from a single in vivodrug-cancer cell interaction experiment have been used to determine the interaction coefficients. The model has then been used to simulate the results of various treatment schedules of the drug on the cancer system, with rather good agreement with experimental data.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1573-8744
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1573-8744
    Keywords: carbon tetrachloride intoxication ; compartments ; liver damage ; Sulfobromo-phthalein kinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract In rats intoxicated by CCl4 (2.5 ml/kg by stomach tube or 10 ml/kg i.m.), the plasma and bile BSP kinetics were fitted to a four-compartment model. The effect of CCl4 was analyzed by the changes brought about in the five transfer constants which characterize the model. Intrahepatic BSP transfer and liver uptake are the parameters most sensitive to CCl4 intoxication. The peak effect is obtained 1 day after the intoxication, with a rapid return to normality.
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  • 5
    Electronic Resource
    Electronic Resource
    Springer
    ISSN: 1573-8744
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Type of Medium: Electronic Resource
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  • 6
    Electronic Resource
    Electronic Resource
    Springer
    ISSN: 1573-8744
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Type of Medium: Electronic Resource
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  • 7
    Electronic Resource
    Electronic Resource
    Springer
    ISSN: 1573-8744
    Keywords: cancer chemotherapy ; cell kinetics ; cell cycle specific drugs ; methotrexate ; cytosine arabinoside ; cyclophosphamide ; cell generation time distribution
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract A general consideration of cancer chemotherapy is presented consisting of a brief description of cell kinetics and some of the biochemical events involved. Models of local tissue and cell uptake of drugs are presented which include various diffusion and mass transport steps. The complex interactions of saturable transport, cell binding, and other pharmacokinetic parameters on the concentration levels of methotrexate in rat bone marrow and other tissues have been studied. A semiquantitative pharmacokinetic model may be used when a critical concentration level of a drug is known. By using a pharmacokinetic model to predict the time that the local drug concentration is above this minimum, one can deduce the extent of cell kill to be expected, as has been done for methotrexate. Jusko (24,25)has developed quantitative models for cell cycle specific drugs such as vinblastine and cytosine arabinoside and non cell cycle specific drugs such as alkylating agents. Himmelstein and Bischoff (26,27)have developed quantitative models which also consider the cell generation time distribution. These models were used to attempt to predict the experimental results for cytosine arabinoside on the mouse L1210 leukemia system.
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  • 8
    ISSN: 1573-8744
    Keywords: pharmacokinetics ; polygenically controlled disease states ; pharmacokinetic twin studies ; pharmacokinetic heritability ; ethanol ; antipyrine ; phenylbutazone ; bishydroxycoumarin.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract The application of pharmacokinetics to the elucidation of polygenic factors involved in drug disposition is discussed in the context of three questions: (a)How extensive is the variation among individuals in rate of plasma clearance for commonly used drugs? (b)If appreciable variation occurs, what are the relative contributions of genetic and environmental factors to its maintenance? (c) What role is played by polygenic factors in maintaining this variation?Large variance in plasma decay rates for phenylbutazone, ethyl biscoumacetate, antipyrine, isoniazid, and nortriptyline is noted throughout the general population. However, these large variations appear to be controlled predominately by genetic rather than by environmental factors on the basis of studies run on identical and fraternal twins. At the present time, an individual's capacity to metabolize drugs and the effects of various conditions in altering that basal, genetically determined capacity seem to be best indicated by measurements of the plasma antipyrine half-life. While the theoretical advantages of obtaining blood concentrations of drugs as a guide to their more rational administration are evident, several practical problems are discussed in this paper.
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  • 9
    ISSN: 1573-8744
    Keywords: disopyramide ; pharmacokinetics ; antiarrhythmic, healthy subjects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Disopyramide exhibits saturable binding to plasma proteins in the therapeutic plasma concentration range. Because of this property, controversy exists in the literature regarding the pharmacokinetic properties of the drug. The purposes of this study were to reassess the pharmacokinetic properties of disopyramide in humans, taking into consideration both total and unbound concentrations and to use disopyramide as a model compound to study the effect of drug binding on the renal clearance of both total and unbound drug. A single intravenous dose of disopyramide (1.5 mg/kg) was administered to eight normal volunteers. Blood and urine samples were collected for 36h. Total concentrations of disopyramide in plasma and urine were determined by high pressure liquid chromatography. Binding of disopyramide to plasma proteins was determined by equilibrium dialysis. In all subjects, the binding of disopyramide to plasma proteins was saturable, but there were considerable differences in binding between subjects. The volume of distribution, total body clearance, and renal clearances of both total and unbound drug were calculated. Because only the total body clearance and renal clearance of unbound compound are not dependent upon unbound fraction (α), these are the only parameters which can be reported without qualification as to the concentration. The mean ± SD total body clearance of unbound drug in the eight subjects was 5.40± 2.80 ml/min/kg. About 50% of this was due to renal elimination. A statistically significant negative correlation of the renal clearance of total disopyramide with time was observed in seven of eight subjects, whereas a significant correlation between the renal clearance of unbound disopyramide and time was observed in only one subject. This suggests that the renal clearance of unbound disopyramide is independent of α, while the renal clearance of total disopyramide is dependent upon α.
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  • 10
    Electronic Resource
    Electronic Resource
    Springer
    ISSN: 1573-8744
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Type of Medium: Electronic Resource
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