摘要:

Very few investigations in man have been specifically devoted to the influence of sex on drug kinetics. Although the potential role of various factors such as the phase of the menstrual cycle, hormonal steroid contraceptive use, menopause or andropause is virtually never taken into account, sex-linked differences in drug kinetics do exist for a limited number of substances such as certain antibiotics, a few tricyclic antidepressants, lithium and aspirin. These sex-linked differences are relatively minor from a quantitative standpoint and appear to be due chiefly to differences in body composition and activity of circulating enzymes and hormones. On the basis of present knowledge, in general these differences in drug kinetics do not warrant modifying dosage as a function of sex.

ISSN:0312-5963    

出版商:ADIS    

年代:1977

数据来源: ADIS

摘要:

Any drug given to a pregnant woman must be considered as possibly harmful to the fetus, since all drugs administered to the mother cross the placental membrane, although at different rates. Important physiological changes occur in pregnancy, which may influence the kinetics of drugs. Differences in gastrointestinal function are likely to alter drug absorption rates in the stomach or gut. Ventilatory alterations modify pulmonary drug absorption or elimination. Important changes in haemodynamics and alterations in body water compartments influence drug distribution and elimination. Renal drug elimination is generally enhanced, whereas hepatic drug elimination may be modified in different ways.Computerised pharmacokinetic models representing the compartmental aspects of the fetalmaternal unit and fetal-maternal drug interrelationships may be used to predict kinetic consequences of fetal drug exposure. Such information may be a useful guide for the clinical use of drugs during pregnancy, particularly for treatment of fetal disease.

ISSN:0312-5963    

出版商:ADIS    

年代:1977

数据来源: ADIS

摘要:

Due in the main to a genetically determined difference in the activity of the liver Nacetyltransferase, a number of primary amine drugs or drug metabolites such as dapsone, isoniazid, hydrallazine, phenelzine, procainamide, sulphadimidine, sulphapyridine and nitrazepam are subject to a bimodal acetylation in man.The population ratio of rapid versus slow acetylators varies widely between ethnic groups throughout the world, apparently being highest in those of an Eastern Asian origin and lowest in Egypt and some Western European countries. With some exceptions, the general clinical consequences of these differences in acetylator phenotype are, if any, that when patients are given a standard dose of the drugs mentioned, the slow acetylators are those who develop most adverse reactions while the rapid acetylators seem more prone to show an inadequate or lack of response to the standard dose.The rationale behind dose adjustments based upon acetylator phenotyping is discussed, and it is tentatively concluded that more precise knowledge about the acetylator phenotype of the actual palient gives a better chance of making drug treatment more optimal from the outset of therapy. However, the possibility that a variety of pathophysiological factors and the concomitant use of other drugs may interfere with acetylator phenotyping has to be considered, as well as some recent evidence that the acetylator phenotype may in itself represent a determinant for the development of certain diseases, like systemic lupus erythematosus and renal failure.

ISSN:0312-5963    

出版商:ADIS    

年代:1977

数据来源: ADIS

摘要:

Diazoxide is given by rapid intravenous injection for the urgent reduction of high blood pressure in patients with all grades of renal function. Oral diazoxide produces less consistent effects. Protein binding of diazoxide is reduced in renal failure and this can be related to reduction of albumin concentration. There is a relation between impairment of renal function and the hypotensive effect of rapidly injected diazoxide. This is explicable in terms of the greater concentration of free (unbound) drug achieved after rapid injection in patients with renal failure. Renal clearance of diazoxide and its metabolites is impaired in renal failure but this is unlikely to affect its activity.

ISSN:0312-5963    

出版商:ADIS    

年代:1977

数据来源: ADIS

摘要:

Significant problems exist in the interpretation of serum digoxin concentration data. Failure to distinguish between results that do not require precise clinical correlation (proof of absorption, presence of drug, etc) and those which depend upon clinical correlation for their meaning (‘toxicity’ or ‘effectiveness’) can result in interpretive errors. Problems relating to the source of the serum digoxin concentration can also confound interpretation. Such difficulty may be controllable (obtaining the sample at the proper time, haemolysis, etc) or related to the laboratory technique (cross-reactivity with digoxin metabolites or other medications, technical errors, or lack of precision).Variation within the same patient over time or between patients related to disease (alterations in electrolytes, adrenergic or parasympathomimetic tone, or other medications) may prevent the direct attribution of an observed phenomenon to a particular digoxin concentration. Techniques for determining the effect of digoxin do exist and can be used to gather data for clinical correlations. Ways of improving the interpretation of serum digoxin concentrations also exist and should be used to improve their value in patient management.The serum digoxin concentration seems to have an important future role. However, we need to know how better to interpret and exploit serum digoxin concentration data.

ISSN:0312-5963    

出版商:ADIS    

年代:1977

数据来源: ADIS

摘要:

Digitoxin is 97% bound to serum albumin and digoxin only to the extent of 24%. Hypoalbuminaemia significantly changes the protein binding of digoxin in Kwashiorkor serum and the binding of digitoxin in patients with chronic active hepatitis and the nephrotic syndrome. Sprue patients with normal albumin values have normal binding of digitoxin. Preliminary data in patients with thyrotoxicosis and myxoedema show digitoxin binding within the normal range.The effect of uraemia per se on digitoxin binding is controversial as both normal and slightly decreased values have been reported. In uraemic patients on treatment with haemodialysis, heparin administration has been shown to be a powerful serum binding displacing agent for both digitoxin and digoxin, the mechanism probably being a heparin-induced release of free fatty acids. Patients with a significant decrease in serum protein binding of digitoxin or digoxin should be maintained on a total serum concentration lower than usually considered within the therapeutic range.

ISSN:0312-5963    

出版商:ADIS    

年代:1977

数据来源: ADIS

ISSN:0312-5963    

出版商:ADIS    

年代:1977

数据来源: ADIS