ISSN:0312-5963    

出版商:ADIS    

年代:1976

数据来源: ADIS

摘要:

Wide variations in drug dose recommendations for children of the same or different ages reflect the inadequacy of data on pharmacokinetics and pharmacodynamics in children. Selected aspects of available literature on pharmacokinetics of drugs used in older infants and children has been reviewed with special attention to calculation of an age-appropriate dose.During the neonatal period and early infancy the elimination of many drugs that are excreted in the urine in unchanged form is restricted by the immaturity of glomerular filtration and renal tubular secretion. On the other hand, in late infancy and/or in childhood, a similar or greater rate of elimination from plasma than in adults has been observed for many drugs, notably digoxin, phenobarbitone, phenytoin, carbamazepine, ethosuximide, diazoxide, clindamycin and propoxyphene. Consistent with this, it has been shown that some drugs exhibit a lower plasma level/dose ratio in infancy and early childhood as compared with the adult. This is true for phenobarbitone, phenytoin and ethosuximide.Some age groups of children remain uninvestigated with regard to pharmacokinetics, even for the drugs reviewed. Therefore, pediatric therapy remains empirically based for many drugs.

ISSN:0312-5963    

出版商:ADIS    

年代:1976

数据来源: ADIS

摘要:

A reduction in plasma albumin concentration, as seen in patients with the nephrotic syndrome, is usually associated with a decrease in plasma protein binding of highly bound drugs. Therefore, the fraction of the unbound drug increases, but the absolute free concentration remains essentially unchanged due to a compensatory reduction in the steady state total plasma concentration. With phenytoin, protein binding and plasma albumin concentration are closely related, so that the degree of binding can be estimated without specific binding techniques. To be able to correctly interprete plasma levels the degree of protein binding should be known, since a reduced total concentration may be fully effective, if the free drug fraction is increased in hypoalbuminaemic patients.Although the mean steady state plasma concentration of highly bound drugs is not affected in the nephrotic syndrome, a greater fluctuation of the unbound level is observed between doses, offering a possible explanation for the increased incidence of toxicity in hypoalbuminaemic patients. As a consequence, shorter dosing intervals of these drugs seems to be advisable, rather than a reduction in the total daily dose.Reduced protein binding is accompanied by an increase in the total plasma clearance which is a function of the elimination rate constant and the volume of distribution.

ISSN:0312-5963    

出版商:ADIS    

年代:1976

数据来源: ADIS

摘要:

The absorption of oral digoxin preparations has been a topic of much concern during the last 5 years. The completeness of digoxin absorption is proportional to the area under the serum concentration time curve and to the urinary excretion of digoxin after single doses. During chronic therapy the completeness of absorption is proportional to these values and also to the steady state serum concentration. Determination of absolute bioavailability of a given digoxin preparation requires a comparative study using intravenous digoxin as a standard.Oral digoxin solutions are incompletely absorbed, but have biological availability greater than or equal to that of tablets. The absorption of digoxin tablets depends upon their dissolution rate which in turn is related to drug particle size. Digoxin tablets with small drug particles have rapid rates of dissolution and can be absorbed as completely as oral solutions. The bioavailability of digoxin from tablets can be influenced by changes in gastro-intestinal motility, malabsorption syndromes, and by co-administration of food or other drugs.New regulations now insure that all marketed digoxin tablet preparations have satisfactory bioavailability. Problems with biological availability at present are unlikely to account for unexpected clinical results during digoxin therapy.

ISSN:0312-5963    

出版商:ADIS    

年代:1976

数据来源: ADIS

摘要:

The plasma concentrations of anticonvulsant drugs, and of certain of their biologically active metabolites, tend to be proportionate to the antiepileptic effects of these drugs. Consequently, anticonvulsant drug levels in plasma are monitored to help guide the clinician in managing his patients' epilepsies. In making use of the measurements, the clinician needs to know the relation between plasma level and biological effect for the various drugs. He also needs to have some awareness of simple pharmacokinetic principles. These are important in deciding when plasma levels should be monitored in relation to the patients' clinical state, to the dosage interval, and to change in the dosage of anticonvulsant or other drug.The clinician also requires pharmacokinetic knowledge in altering anticonvulsant drug dosage in his patients, and in interpreting plasma anticonvulsant level data, particularly when the patient is concurrently suffering from non-neurological disease. The ability to monitor plasma anticonvulsant levels has appreciably improved the treatment of epilepsy, but to obtain maximum benefits from the method, both pharmacokinetic insight and clinical wisdom are required.

ISSN:0312-5963    

出版商:ADIS    

年代:1976

数据来源: ADIS

摘要:

Computer programs for drug dosage adjustment may be fixed, adaptive or empirical.The aminoglycoside antibiotic dosage requirements of individual patients are relatively predictable, and it seems to be adequate to assume that volume of distribution is a fixed proportion of body weight and that renal clearance is a fixed proportion of creatinine clearance. This approach has been less successful with digoxin because patient compliance, the proportion absorbed and liver clearance are not yet predictable. Accordingly, adaptive programs have been developed which use feedback from drug concentration measurements to predict the future dosage needs of the patient.When individual needs are known for a large patient group it becomes possible to predict the dosage requirements of a new patient from the same population by empirical methods. Computer programs for dosage adjustment will not be widely used until their scope is increased and objective evidence of clinical benefit is obtained.

ISSN:0312-5963    

出版商:ADIS    

年代:1976

数据来源: ADIS

ISSN:0312-5963    

出版商:ADIS    

年代:1976

数据来源: ADIS