摘要:

Dosage schedules of procainamide should be individualised, because the amount of the drug required to control ventricular tachyarrhythmias varies widely among patients. Individual differences in procainamide pharmacokinetics are responsible for most of this variation and are reflected by the serum concentration of the drug. Procainamide concentrations in serum and in myocardial interstitial fluid must equilibrate rapidly and be similar at equilibrium. The effects of the drug on the myocardial cell membrane are proportional to the concentration at that site, develop quickly and are readily reversible. Accordingly, there is a useful relation between the serum concentration and the intensity of cardiac action of procainamide.Procainamide serum levels are most helpful for adjusting dosage schedules in patients whose response to the drug is difficult to evaluate or appears to be abnormal. Serum concentrations of 4 to 10mg/litre correct and prevent over 90% of ventricular tachyarrhythmias responsive to procainamide without causing important adverse effects. Lower concentrations are partially effective in some patients. Additional therapeutic benefit is rarely obtained by raising the serum level above 10mg/litre, and serious toxicity becomes increasingly common above 12mg/litre. Serum concentration information must always be interpreted in the light of all other clinical information, since the type of arrhythmia and many other factors influence the response of the heart to procainamide.N-Acetylprocainamide, a metabolite of procainamide, possess antiarrhythmic activity and is not measured by the usual methods for determining serum procainamide. The concentration ratio of drug and metabolite in serum varies greatly among patients, and their potency ratio against various ventricular dysrhythmias in man remains in question. By measuring Nacetylprocainamide as well as procainamide, it may ultimately be possible to define a therapeutic range of the sum of the appropriately weighted concentrations of the 2 compounds. For the present, the therapist must rely primarily on the serum concentration of procainamide for supplementing his clinical judgment.

ISSN:0312-5963    

出版商:ADIS    

年代:1977

数据来源: ADIS

摘要:

The factors affecting solute movement across the membrane during haemodialysis are well understood. Likewise the mathematics of drug kinetics are well described. However, studies of the effects of artificial kidneys on drug kinetics have often been limited by a lack of attention to proper methods of calculating solute clearance by the artificial kidney.

ISSN:0312-5963    

出版商:ADIS    

年代:1977

数据来源: ADIS

摘要:

During pregnancy a number of continuously changing circumstances exist which might be expected to modify the relation between plasma drug levels and drug dosage. Alimentary tract motility may be decreased, the distribution of many drugs may be altered, glomerular filtration rate is greater and biotransformation capacity may be changed as pregnancy advances. However, relatively little has been published on the monitoring of plasma drug levels during pregnancy.It has been established that, in the presence of constant drug doses, plasma levels of phenytoin, phenobarbitone and certain other anticonvulsants tend to fall during pregnancy and rise again during the puerperium. Plasma lithium and possibly digoxin levels also fall relative to drug dose as pregnancy progresses, and rise again in the puerperium.While the changes in lithium and digoxin levels are probably chiefly due to increased rate of glomerular filtration during pregnancy, the altered anticonvulsant requirement is more likely to depend mainly on an increased rate of biotransformation. Anticonvulsant plasma levels should be monitored regularly from the outset of pregnancy and more frequently after birth.

ISSN:0312-5963    

出版商:ADIS    

年代:1977

数据来源: ADIS

摘要:

The major difficulty in using pharmacokinetic concepts for monitoring individual therapy with 5-fluorouracil is based on the mostly intracellular location of the active nucleotide metabolites of 5-fluorouracil with no clear correlation to plasma levels of the drug. In addition, the basic biochemical mechanism of ‘thymine-less cell death’ following inhibition of de novo thymidylate synthesis by 2′-deoxy-5-fluorouridine 5′-monophosphate (FdUMP) is poorly understood, and only some of the biochemical determinants of therapeutic response to 5-fluorouracil are known. Individualised therapy with 5-fluorouracil requires an integrated approach which should include methods of pharmacokinetics and biochemical kinetics. 5-Fluorouracil stands as an example for most of the pyrimidine and purine metabolites to which similar considerations apply in monitoring of cancer chemotherapy.

ISSN:0312-5963    

出版商:ADIS    

年代:1977

数据来源: ADIS

摘要:

In a cross-over study, the oral absorption following equimolar doses of ampicillin corresponding to 16.7mg/kg administered as pivampicillin (‘Pondocillin’) suspension and ampicillin (‘Doktacillin’) suspension respectively, was investigated in 11 children aged from 8 months to 4.5 years. Pivampicillin produced a mean peak serum concentration of 10.7&mgr;g ampicillin/ml compared with 5.8&mgr;g/ml after ampicillin. The mean area under the serum concentration-time curves was 29.2&mgr;g/ml · h after pivampicillin and 16.7&mgr;g/ml · h after ampicillin, reflecting the superior bioavailability of the ester form.In 4 of the children aged between 8 and 12 months, the serum levels after pivampicillin were consistently lower than those recorded in the remaining 7 children beyond the age of 1 year. The mechanism and therapeutic implications of this finding require further study.

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