ISSN:0312-5963    

出版商:ADIS    

年代:1992

数据来源: ADIS

摘要:

Endocrine therapy is important in the treatment of advanced breast cancer. The prototype antiestrogen tamoxifen and the prototype aromatase inhibitor aminoglutethimide have been in clinical use for more than 2 decades, as have synthetic progestin derivatives. Currently, several novel antiestrogens and aromatase inhibitors are used to treat breast cancer. This paper reviews the present knowledge of the clinical pharmacokinetics of these drugs. Drug monitoring in plasma and other body fluids has been improved over recent years by the introduction of sensitive and specific high performance liquid chromatography and gas chromatography-mass spectrometry methods. However, we still lack information on such basic pharmacokinetic parameters as the bioavailability of several of these drugs. It is important to study not only plasma but also tissue drug concentrations.

ISSN:0312-5963    

出版商:ADIS    

年代:1992

数据来源: ADIS

摘要:

Heparin was discovered approximately 75 years ago and has been used extensively for the last 50 years to treat thromboembolic disorders. An endogenous glycosaminoglycan, heparin is found largely in the liver, lung and intestine. It is available for exogenous administration both as unfractionated and low molecular weight heparin. Unfractionated heparin is a heterogenous mixture of polysaccharide chains of varying length resulting in a range of molecular weights from 3000 to 30 000D while low molecular weight heparin ranges from 3000 to 6000D. Heparin produces its antithrombotic effect by binding to antithrombin III and this complex then binds to thrombin. In order to accomplish this a total of 18 to 22 monosaccharide units is necessary including a specific pentasaccharide binding site for antithrombin III. After either subcutaneous or intravenous injection heparin is distributed primarily within the intravascular space. A short distribution phase is seen which is thought to correspond to endothelial cell binding and internalisation. The disposition curve for unfractionated heparin has a unique concave-convex shape which is the result of combined saturable and nonsaturable elimination mechanisms. The nonsaturable elimination mechanism is renal and is the primary route of elimination for low molecular weight heparins. For this reason, the concave-convex pattern is not seen with low molecular weight preparations. Both forms of heparin are useful antithrombotic agents; however, the correlation between the antithrombotic effect and anin vitrolaboratory test for either type still needs further clarification.

ISSN:0312-5963    

出版商:ADIS    

年代:1992

数据来源: ADIS

摘要:

Angiotensin converting enzyme (ACE) inhibitors are increasingly used to treat hypertension and congestive heart failure. Recently, several new ACE inhibitors with pharmacokinetic features different from earlier agents such as captopril or enalapril have come into use. This review discusses the use of pharmacokinetics to optimise ACE inhibitory therapy in various patient groups.Among the pharmacokinetic characteristics of ACE inhibitors the route of excretion and to a lesser degree the half-life appear to be the most clinically relevant. There is no evidence that being a prodrug offers a significant clinical advantage. The importance of varying tissue penetration also remains to be determined.Knowledge of ACE inhibitor pharmacokinetics is particularly important in patients with renal or hepatic dysfunction in whom the major route of excretion of these agents is impaired. This might also be the case in elderly patients or those with severe congestive heart failure. However, for most ACE inhibitors, major changes in the drug dosage (amount or interval) are necessary only when the glomerular filtration rate falls below 30 ml/min (1.80 L/h).The occurrence of adverse effects due to overdosage or drug interactions may be prevented by adapting the prescription of an ACE inhibitor to its pharmacokinetic characteristics.

ISSN:0312-5963    

出版商:ADIS    

年代:1992

数据来源: ADIS

摘要:

The pharmacokinetics of Factor VIII procoagulant activity (FVIII:C) were investigated in 10 patients receiving 2 different high purity concentrates of FVIII. Thein vivorecovery of FVIII:C depended on the method of blood volume estimation and on thein vitroassay used to define the potency of the concentrate; more generally, it also depends on the study design. The use ofin vivorecovery to compare FVIII preparations should therefore be discouraged and the achieved area under the FVIII activity-time curve (AUC) should be used instead.The volume of distribution at steady-state (Vss) of FVIII:C was significantly greater than the estimated plasma volume of the patients. The mean terminal half-life of FVIII:C was slightly assay-dependent, being 14h by a 1-stage clotting assay and 12h by a chromogenic assay. The calculated apparent clearance (CL) of FVIII:C, as well as the Vssand thein vivorecovery, depended on the measuredin vitropotency of the FVIII concentrate.These methodological aspects of pharmacokinetic studies are of direct interest to the clinician, since the routine administration of FVIII is based on the pharmacokinetic properties of the specific preparation.

ISSN:0312-5963    

出版商:ADIS    

年代:1992

数据来源: ADIS

摘要:

A pharmacokinetic model was designed to describe simultaneously the plasma concentrations of atracurium and its metabolite laudanosine. The proposed model satisfactorily fits the observations and is based on the assumptions that the parent drug spontaneously degrades to laudanosine at the rate comparable with that observedin vitroat pH 7.4 and 37°C; that 2 molecules of laudanosine are formed from 1 molecule of atracurium; that an initial very rapid decay of a fraction of the atracurium dose is responsible for the initially high plasma laudanosine concentrations; that the rapid disappearance of atracurium from plasma is accounted for by its spontaneous degradation and by the sequestration of atracurium in a deep compartment; and that laudanosine formed from atracurium is added to its central compartment, with its disposition described by a simple 2-compartment model with elimination from the central compartment. The model projects that about 43% of the atracurium dose is rapidly converted to laudanosine and that nearly the whole injected amount of atracurium is degraded to laudanosine.

ISSN:0312-5963    

出版商:ADIS    

年代:1992

数据来源: ADIS