ISSN:0163-4356    

出版商:OVID    

年代:1980

数据来源: OVID

摘要:

The impact of drug level monitoring on practice and quality of therapy is discussed. Analysis of the literature and a more detailed discussion of three model drugs (salicylates, digoxin, and theophylline) show a surprisingly low degree of attention to the problem of evaluating the clinical relevance of a drug monitoring program through controlled studies and techniques. There is a potential, and possibly already existing, gap between clinical pharmacokinetics and routine therapy. Closer assessment of these points, with emphasis on educational programs, should be considered among the frontiers leading to a better integration of therapeutic monitoring into medical practice.

ISSN:0163-4356    

出版商:OVID    

年代:1980

数据来源: OVID

摘要:

Basic definitions, theoretical considerations, and practical aspects of routine therapeutic drug monitoring are discussed, with emphasis on the desirability of measuring the pharmacodynamic effects of a drug rather than its plasma concentrations. The advantages and problems of this approach are reviewed for a number of specific drugs and drug classes: digitalis, beta-blockers, antihypertensives, and antiarrhythmic agents.

ISSN:0163-4356    

出版商:OVID    

年代:1980

数据来源: OVID

摘要:

Monitoring plasma concentrations of therapeutic drugs presents special problems when these drugs are metabolized to compounds that have pharmacologic activity. This presentation reviews several methods for evaluating the pharmacologic activity of drug metabolites and describes the impact of active drug metabolites on the pharmacokinetic design of dose regimens and on the formulation of guidelines for plasma level interpretation. Lidocaine and monoethylglycinexylidide illustrate the considerations that pertain when both a drug and its active metabolite have similar therapeutic and toxic actions. Procainamide andN-acetylprocainamide exemplify the much more complex situation that arises when a drug and its active metabolite have different pharmacologic activity.

ISSN:0163-4356    

出版商:OVID    

年代:1980

数据来源: OVID

摘要:

Aspects of measurement of plasma protein-binding of drugs and the representation and interpretation of such data, together with the effect of altered binding on pharmacokinetics and the impact on therapeutic plasma drug concentration monitoring, are reviewed. In most instances, altered binding affects interpretation of plasma concentration data rather than causes a need for a change in the usual dosage regimen.

ISSN:0163-4356    

出版商:OVID    

年代:1980

数据来源: OVID

摘要:

Measurements of concentrations for drugs from plasma or biological fluids taken together with the clinical status of the newborn infant may provide better assurance of avoiding potentially dangerous over- or underdosing. They are also useful as guidelines in requisite clinical trials and study designs. To the developmental biologist and pharmacologist, they serve as potent biological probes for various events underlying biochemical differentiation or maturation in the human fetus and newborn infant. Future research developments in neonatal drug monitoring should include improvement of micro-methods for drug assays and refinement of noninvasive techniques for monitoring drug concentrations from biological fluids and for evaluation of drug effects.

ISSN:0163-4356    

出版商:OVID    

年代:1980

数据来源: OVID

摘要:

Therapeutic drug monitoring of serum concentrations has become a rapidly expanding area of clinical pharmacology and is likely to remain an important growth area in the future, despite that the evidence for the efficacy of such monitoring is inconclusive except for a handful of drugs and findings that the reliability of much drug assay work is far from optimal. Nonetheless, in view of the likelihood that the use of routine monitoring will increase, the institution of quality control programs seems not only desirable, but necessary. We describe the design of Bartscontrol (formerly known as St. Bartholomew's Hospital Quality Control Scheme for Antiepileptic Drugs) and discuss the experience of this program. Although the feedback provided to the participants of such a program seems to encourage an overall increase in precision, our findings also indicate that some laboratories perform consistently badly. While the data generally do not reveal that variations in precision are due to analytical method employed, a scheme such as the one described can occasionally make the important finding that a particular technique is inappropriate, as was found for the case of spectrophotometry for phenytoin.

ISSN:0163-4356    

出版商:OVID    

年代:1980

数据来源: OVID

摘要:

Valproic acid, a new type of antiepileptic drug, has developed into one of the drugs of first choice in all types of epilepsy with the exception of infantile spasms and partial seizures. Due to its short biological half-life, a steady-state plasma concentration will be reached rapidly after initiation of therapy. However, no direct relationship between this plasma concentration and the clinical effect can be found. In autoradiography experiments, brain distribution appears to change with time, suggesting a gradual accumulation of the drug or its metabolites in certain brain areas. Two metabolites are detected in monkey and human blood plasma. Valprolactone is also found in brain tissue, but the substance is rapidly eliminated. β, γ-Unsaturated valproic acid has the longest half-life and is found in concentrations that can be quantitated by routine gas chromatographic analysis. The therapeutic effect appears to correlate better with dosage per kilogram body weight than with the actual plasma concentrations. Routine monitoring of valproate plasma concentrations in epileptic patients seems to be of limited value.

ISSN:0163-4356    

出版商:OVID    

年代:1980

数据来源: OVID

摘要:

Lithium therapy has become generally accepted as one of the major regimens for the treatment of acute mania as well as for the prevention of relapse in recurrent bipolar mood disorders. It is one drug for which monitoring is understood to be crucial, since the drug (1) has broad interindividual variability in dose-response, (2) often has a very narrow intraindividual therapeutic concentration index, (3) has a broad interindividual distribution of sensitivity and tolerance, and (4) is extremely dependent on stable kidney function for its successful and safe use. Determination of serum lithium concentration is the most important monitoring technique. However, the need for standardized clinical procedure coupled with corresponding reference ranges remains to be satisfied. The 12 hr standardized serum lithium is seen as the answer to this need, and the specifics of and indications for the procedure and appropriate reference values are given. The therapeutic range is suggested to lie between 0.30 and 1.30 mmoles/liter, with 1.50 mmoles/liter representing the lower limit of risk for intoxication. The treatment of initial and intercurrent lithium intoxication, which can reach life-threatening proportions, is also described.

ISSN:0163-4356    

出版商:OVID    

年代:1980

数据来源: OVID

摘要:

As a result of their slow onset of action, the difficulty of assessing dose-effect, and the marked interindividual variability of steady-state plasma concentration, tricyclic antidepressants present a special challenge, as well as opportunity, for therapeutic drug monitoring. As shown particularly by the twin studies of Alexanderson, the most important factor responsible for interindividual variation is metabolism; in comparison, differences in binding to plasma proteins are much less significant. Despite the problems posed by the complexity of action of tricyclic antidepressants and their active metabolites on noradrenaline and serotonin metabolism and on monoaminergic receptor sites — as well as the heuristic difficulty calling for a combination of analytical, clinical, pharmacological, and psychiatric expertise — some headway is being made in our understanding the responses of patient populations to this family of drugs. The following conclusions are drawn: (a) monitoring of the plasma concentration of some tricyclics in some types of depressives may improve the clinical use of these drugs; (b) such measurements are valuable mainly in non-responders to normal therapeutic doses; and (c) there seem to exist biochemical subgroups of depressive patients for whom drug choice must be tailored.

ISSN:0163-4356    

出版商:OVID    

年代:1980

数据来源: OVID