ISSN:0312-5963    

出版商:ADIS    

年代:1995

数据来源: ADIS

ISSN:0312-5963    

出版商:ADIS    

年代:1995

数据来源: ADIS

摘要:

Tacrolimus, a novel macrocyclic lactone with potent immunosuppressive properties, is currently available as an intravenous formulation and as a capsule for oral use, although other formulations are under investigation.Tacrolimus concentrations in biological fluids have been measured using a number of methods, which are reviewed and compared in the present article. The development of a simple, specific and sensitive assay method for measuring concentrations of tacrolimus is limited by the low absorptivity of the drug, low plasma and blood concentrations, and the presence of metabolites and other drugs which may interfere with the determination of tacrolimus concentrations. Currently, most of the pharmacokinetic data available for tacrolimus are based on an enzyme-linked immunosorbent assay method, which does not distinguish tacrolimus from its metabolites.The rate of absorption of tacrolimus is variable with peak blood or plasma concentrations being reached in 0.5 to 6 hours; approximately 25% of the oral dose is bioavailable. Tacrolimus is extensively bound to red blood cells, with a mean blood to plasma ratio of about 15; albumin and &agr;1-acid glycoprotein appear to primarily bind tacrolimus in plasma. Tacrolimus is completely metabolised prior to elimination. The mean disposition half-life is 12 hours and the total body clearance based on blood concentration is approximately 0.06 L/h/kg. The elimination of tacrolimus is decreased in the presence of liver impairment and in the presence of several drugs.Various factors that contribute to the large inter- and interindividual variability in the pharmacokinetics of tacrolimus are reviewed here. Because of this variability, the narrow therapeutic index of tacrolimus, and the potential for several drug interactions, monitoring of tacrolimus blood concentrations is useful for optimisation of therapy and dosage regimen design.

ISSN:0312-5963    

出版商:ADIS    

年代:1995

数据来源: ADIS

摘要:

Zopiclone is a cyclopyrrolone hypnotic agent. It possesses a chiral centre and is commercially available as a racemic mixture. Methods involving high performance liquid chromatography (HPLC), gas chromatography, capillary electrophoresis (CE) and high performance thin layer chromatography have been developed for the quantitation of zopiclone and its 2 main metabolites in biological samples. For the chiral determination of the enantiomers of zopiclone and its metabolites, HPLC and CE methods are available.After oral administration, zopiclone is rapidly absorbed, with a bioavailability of approximately 80%. The plasma protein binding of zopiclone has been reported to be between 45 and 80%. Zopiclone is rapidly and widely distributed to body tissues including the brain, and is excreted in urine, saliva and breast milk.Zopiclone is partly metabolised in the liver to form an inactiveN-demethylated derivative and an activeN-oxide metabolite. In addition, approximately 50% of the administered dose is decarboxylated and excreted via the lungs. Less than 7% of the administered dose is renally excreted as unchanged zopiclone. In urine, theN-demethyl andN-oxide metabolites account for 30% of the initial dose. The terminal elimination half-life (t½z) of zopiclone ranges from 3.5 to 6.5 hours.The pharmacokinetics of zopiclone in humans are stereoselective. After oral administration of the racemic mixture, Cmax(time to maximum plasma concentration), AUC (area under the plasma time-concentration curve) and t½zvalues are higher for the dextrorotatory enantiomer owing to the slower total clearance and smaller volume of distribution (corrected by the bioavailability), compared with the levorotatory enantiomer. In urine, the concentrations of the dextrorotatory enantiomers of theN-demethyl andN-oxide metabolites are higher than those of the respective antipodes.The pharmacokinetics of zopiclone are altered by aging and are influenced by renal and hepatic functions. Drug interactions have been observed with erythromycin, trimipramine and carbamazepine.

ISSN:0312-5963    

出版商:ADIS    

年代:1995

数据来源: ADIS

摘要:

Pharmacokinetic monitoring is not routine in the treatment of psychiatric disorders, although subtherapeutic or toxic plasma concentrations of psychotropic agents can result from standard doses because of interindividual variability of drug metabolism. Therapeutic plasma concentrations have been established for several of the tricyclic antidepressants and for lithium, as well as for carbamazepine and valproic acid (valproate sodium). Despite difficulties in extrapolating from concentration-effect research, therapeutic concentrations have also been determined for some antipsychotic drugs, in particular haloperidol and clozapine.Clinicians can use therapeutic drug monitoring to optimise dosage decisions with psychotropic drugs, in order to maximise efficacy and prevent toxicity, especially when individuals are nonresponsive to treatment or vulnerable to adverse reactions with standard doses because age, disease states or drug interactions complicate therapy. Although evidence from controlled-outcome studies is unavailable, TDM-assisted psychiatric treatment is potentially useful and cost effective, particularly when applied by clinicians who are knowledgeable of pharmacokinetics and who are aware of the limitations of laboratory findings.

ISSN:0312-5963    

出版商:ADIS    

年代:1995

数据来源: ADIS