Biomedical subjects
H Kurz
Publications and source records attributed to H Kurz.
[Electro-focal diagnosis--reality or hypothesis?].
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Binding of drugs to muscle tissue: dependence on drug concentration and lipid content of tissue.
For a series of 16 drugs the extent of binding to homogenized rabbit skeletal muscle was determined by means of ultrafiltration. The percent bound of basic drugs was essentially constant over a 100- to 1000-fold concentration range, i.e., binding was linear. Among weak organic acids the fraction bound decreased with increasing drug concentration for furosemide, warfarin, phenylbutazone, salicyclic acid and sulfonamides. Fitting of the binding data by Langmuir isotherms appeared to be inappropriate for several reasons. A simple power function (Freundlich isotherm) was found to satisfactorily represent the experimental data. Drug binding properties of muscle homogenate were altered following extraction of lipids with acetone. Lipid-depleted muscle tissue exhibited a decrease in binding of chlorpromazine and propranolol, whereas binding of imipramine was unchanged. Binding of phenytoin, warfarin and sulfadimethoxine was enhanced in lipid-depleted muscle. The results suggest that binding of drugs to muscle tissue cannot solely be explained in terms of partitioning into lipids.
Binding of drugs to human muscle.
Binding of 22 drugs to human muscle tissue has been determined by ultrafiltration. All drugs tested were bound, the bound fraction ranging from 13% (aminophenazone) to greater than 98% (desipramine). Both linear and nonlinear binding was observed. For chemically related substances, binding to muscle tissue correlated with plasma binding and lipid solubility. There were significant differences in binding to muscle from different individuals. With respect to pharmacokinetics of drugs, it is suggested that binding to muscle tissue may be at least as important as plasma binding.
[Pharmaco-kinetic aspects of protein-binding (author's transl)].
Binding of drugs to plasma proteins will influence distribution and elimination especially if factors interfere altering the extent of binding. These factors are: dependence on species, age, H+-concentration, speed of i.v. injection or the interaction of another drug for instance. Considering the quantitative aspects changes in binding to the plasma proteins will turn only then relevant to drug action if the extent of alteration is very large or the drugs are bound to a very high degree. But the scene changes completely if the binding to other proteins of the organism is considered. Experimental results concerning the binding of drugs to hemoglobin and muscle tissue suggest that this kind of binding is possibly more effective in pharmacokinetics than binding to plasma proteins.
Differences in the binding of drugs to plasma proteins from newborn and adult man. I.
The binding of various drugs to plasma proteins from adult and cord plasma was determined by equilibrium dialysis. For almost all the drugs binding to cord plasma was lower than to plasma from adults. No evidence was found that the difference in binding was due to the different protein concentration in cord and adult plasma or to an influence of substances in ultrafiltrates of the plasmas.
Differences in the binding of drugs to plasma proteins from newborn and adult man. II.
The binding of certain drugs to isolated fractions of plasma proteins obtained from newborn and adult man has been studied by equilibrium dialysis. For thiopental, desipramine, nitrofurantoin, sulfamethoxydiazine, meticillin and salicylic acid no difference was found between binding to the albumin fraction from newborns and adults. However, for thiopental, desipramine and promethazine binding to the globulin fraction was smaller in the newborns than in adults. Addition of bilirubin to the albumin fraction decreased the binding of nitrofurantoin, sulfamethoxydiazine and meticillin. No difference in the binding of meticillin to the albumin or globulin fractions from newborns and adults was found. The binding decreased, however, if both fractions were combined. Four mechanisms to explain the difference in binding between newborns and adults are discussed: (1) Displacement of drugs by bilirubin, (2) different binding properties of cord and adult albumin, (3) different properties of the globulins and (4) interaction of albumin with globulins in the newborn.
[Drug accumulation and dose finding (authors' transl)].
Accumulation following repeated doses is no individual behavior of a drug, but always happens if the rate of invasion of a drug exceeds its rate of evasion. Using parameters such as dosing interval and biological half-life of a drug, its rate of accumulation as well as the equilibrium drug concentration in the body can be calculated. The initial dose and the maintenance dose can be calculated in a similar way. For an individual case the reliability of data calculated on the basis of mean values for biological halflife may be limited by the statistical variation of means and by factors altering the elimination of the drug, e.g. pathological changes or the influence of drugs given additionally. Nevertheless, these data may serve as a guidance to the physician to help him find the individual dosage for his patient.
Evaluation of methods to determine protein-binding of drugs. Equilibrium dialysis, ultrafiltration, ultracentrifugation, gel filtration.
The reliability of the most important methods to determine protein-binding of drugs was compared. Applying these methods to different drugs solved in bovine plasma or in protein-free solutions the incidence of errors specific for each method was examined. Certain limits are found for the applicability of each method. If these limitations are observed reproducibility differs only slightly within the four methods. Considering all the results, however, the values achieved by equilibrium dialysis appear to come closest to the real extent of binding.
Alteration of protein-binding during storage of human plasma preparations.
The influence of the storage of plasma preparations on binding was studied in different drugs. No alteration on only a slight alteration of binding was found if the plasma preparations were kept deep-frozen, or at temperatures between +3 degrees and +4 degrees C, for up to 12 months. More marked changes were found for some drugs if the plasma preparations were lyophilized or stored at +32 degrees C, for 6 and 12 months.
Proceedings: Factors responsible for different binding of drugs to plasma proteins of newborn and adults.
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Proceedings: Influence of the hydrophobic quality of a drug on its absorption from the rectum of rats.
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[Relations between the permeation of drugs across the blood-cerebrospinal fluid barrier and their distribution in different lipid-water models].
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[Influence of protein binding on the distribution of drugs after rapid and slow injection].
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[Changes in the binding properties of plasma proteins in plasma stored under various conditions].
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The permeation of drugs across the placental barrier.
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[Differences between the protein binding of newborns and adults and their importance for pharmacological action].
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[Influence of acidosis and alkalosis on the binding of drugs to plasma proteins].
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