ISSN:0312-5963    

出版商:ADIS    

年代:1992

数据来源: ADIS

ISSN:0312-5963    

出版商:ADIS    

年代:1992

数据来源: ADIS

摘要:

Ketorolac is a new chiral nonsteroidal anti-inflammatory drug (NSAID) which is marketed for analgesia as the racemate. The drug is administered as the water soluble tromethamine salt and is available in tablets or as an intramuscular injection. The absorption of ketorolac is rapid, Cmaxbeing attained between 20 to 60 min. Its oral bioavailability is estimated to range from 80 to 100%. The drug is extensively bound (>99%) to plasma proteins and has a volume of distribution (0.1 to 0.3 L/kg) comparable with those of other NSAIDs. Only small concentrations of ketorolac are detectable in umbilical vein blood after administration to women in labour. The elimination half-life is between 4 and 6h and is moderate in comparison with other NSAIDs. The area under the plasma concentration-time curve of ketorolac is proportional to the dose after intramuscular administration of therapeutic doses to young healthy volunteers.Ketorolac is extensively metabolised through glucuronidation and oxidation; little if any drug is eliminated unchanged. Most of the dose of ketorolac is recovered in the urine as conjugated drug. Although ketorolac is excreted into the breast milk, the amount of drug transferred comprises only a small fraction of the maternal exposure. Little stereoselectivity was present in the pharmacokinetics of ketorolac in a healthy volunteer receiving single intravenous or oral doses. The elderly exhibit reduced clearance of the drug. Renal insufficiency appears to cause an accumulation of ketorolac in plasma, although hepatic disease may not affect the pharmacokinetics.

ISSN:0312-5963    

出版商:ADIS    

年代:1992

数据来源: ADIS

摘要:

The efficacy of cyclosporin as an immunosuppressive agent is largely based on clinical indicators such as graft survival, rejection or nephrotoxicity. Therapeutic monitoring is necessary to evaluate the efficacy of cyclosporin therapy. The most widely used method for monitoring cyclosporin therapy is the measurement of predose trough blood concentrations of the drug. The relationship of a single or multiple blood cyclosporin concentration to slowly evolving outcomes is difficult to establish. Some investigators have found a good correlation between cyclosporin trough concentrations on the one hand and cyclosporin toxicity and rejection on the other, but others have not.Therapeutic monitoring of cyclosporin may be enhanced using some biological assays for immunosuppression (pharmacodynamic monitoring) in addition to cyclosporin trough concentrations (pharmacokinetic monitoring). However, direct monitoring of the immune response to cyclosporin therapy using a clinically applicable biological assay is difficult. Some pharmacodynamic parameters have been suggested as biological markers in the clinical monitoring of cyclosporin.

ISSN:0312-5963    

出版商:ADIS    

年代:1992

数据来源: ADIS

摘要:

The available techniques for the investigation of drug binding to plasma and tissues protein are reviewed and the advantages and disadvantages of the various techniques stated. A comparison of different plasma protein binding techniques is made which shows that the size of the unbound fraction of drug may be influenced by the method used. Protein binding may be assayed by methods including equilibrium dialysis, ultrafiltration, ultracentrifugation, gel filtration, binding to albumin microspheres and circular dichroism. Tissue binding techniques can involve testing binding to isolated organs, tissue slices, homogenates and isolated subcellular particles. Details of the available methods to compute pharmacokinetic constants are given. Stereoselective binding has been investigated for a limited number of drugs and the difference in the binding of 2 enantiomers is usually modest. The measurement of the binding constants is often required to characterise the drug-protein interaction. Mathematical and graphical methods to compute the pharmacokinetic parameters are discussed. The implications of binding on the volume of distribution and clearance of drugs are examined.

ISSN:0312-5963    

出版商:ADIS    

年代:1992

数据来源: ADIS

摘要:

The pharmacokinetics of omeprazole and its metabolites were studied in 8 healthy elderly volunteers using [14C]omeprazole. In another 6 healthy elderly volunteers, the pharmacokinetics of omeprazole were studied using unlabelled drug. Each volunteer received single doses of omeprazole intravenously (20mg) and orally (40mg) as solutions in a randomised crossover design. The plasma concentrations and urinary excretion of omeprazole and metabolites were followed for 24 and 96h, respectively.The results indicate that the average metabolic capacity of omeprazole is decreased in the elderly compared with that found in earlier studies of healthy young individuals. This was reflected in an increase in bioavailability from 56 to 76%, a reduction in mean systemic clearance by approximately 50% (0.25 L/min) and a prolongation of the mean elimination half-life from 0.7 to 1.0h compared with the young.Despite these findings, the considerable overlap in these parameters between young and old volunteers, together with data from previous pharmacodynamic studies and the wide therapeutic range of omeprazole, indicate that dosage reductions are not needed in the elderly.

ISSN:0312-5963    

出版商:ADIS    

年代:1992

数据来源: ADIS

摘要:

The potential for pharmacokinetic interactions between moxonidine and digoxin at steady-state was investigated in 15 healthy male volunteers. Multiple oral doses of 0.2mg moxonidine twice daily and 0.2mg digoxin once daily were administered alone and in combination in a randomised 3-period crossover design. The drugs were administered for at least 5 days.The results indicate that neither moxonidine nor digoxin influences the pharmacokinetics of the other drug under steady-state conditions.

ISSN:0312-5963    

出版商:ADIS    

年代:1992

数据来源: ADIS