ISSN:0312-5963    

出版商:ADIS    

年代:1992

数据来源: ADIS

摘要:

The calcium antagonists are valuable and widely used agents in the management of essential hypertension and angina. There is an increasing number of new agents to add to the 3 prototype substances nifedipine, diltiazem and verapamil. These new agents are dihydropyridines structurally related to nifedipine. However, they tend to have longer elimination half-lives (t½&bgr;) and may be suitable for twice-daily administration. Amlodipine is an exception with a t½&bgr;in excess of 30h. Apart from elimination rates, however, the pharmacokinetic characteristics of the newer agents have a notable tendency to resemble those of the established agents. They are highly cleared drugs, are relatively highly protein bound. As they are subject to significant first-pass metabolism, old age and hepatic impairment will increase their plasma concentrations due to a reduced firstpass effect. Renal impairment does little to their pharmacokinetics since the fraction eliminated unchanged by the kidney is small. For most agents, plasma concentration-response relationships have been described. Interesting areas for further research include chronopharmacokinetics, stereoselective pharmacokinetics and lipid solubility. Drugs affecting hepatic blood flow and drug metabolising capacity have predictable interaction potential. Some of the newer calcium antagonists will, like verapamil, increase plasma digoxin concentrations. Verapamil and diltiazem decrease phenazone (antipyrine) metabolism and therefore tend to decrease the metabolism of other drugs.

ISSN:0312-5963    

出版商:ADIS    

年代:1992

数据来源: ADIS

摘要:

Renal insufficiency is characterised by impaired host defences, which are compromised further by each of the 3 modes of renal replacement - haemodialysis, continuous ambulatory peritoneal dialysis (CAPD) and renal transplantation. Reduced renal clearance of unknown toxins, possible development of nutritional deficiencies and administration of immunosuppressive medications lead to aberrant immune regulation early in the course of renal failure. This results subsequently in increased frequency and severity of infection. Vaccination plays an important role in attenuating this infection risk, but impaired cell-mediated and humoral immunity contraindicates the use of live vaccines and engenders suboptimal and short-lived antibody responses to inactivated vaccines. Reinforced vaccination schedules, increased vaccine dosage and concomitantly administered adjuvant immunomodulators have variably improved the defective antibody responses to certain vaccines.Immunisation against hepatitis B virus has resulted in a significant decrease in prevalence and incidence of this infection in haemodialysis units. Similarly, the inoculation of influenza vaccine in patients with uraemia and of polyvalent pneumococcal vaccine in special risk circumstances has been recommended because of perceived reductions in morbidity and mortality from infection with these agents. Cytomegalovirus (CMV) vaccine may attenuate CMV disease severity in recipients of renal allografts.Staphylococcus aureusvaccine, on the other hand, is ineffective in preventing peritonitis or exit site infections in patients receiving CAPD. Other killed vaccines have not been comprehensively studied, but generally have the same indications for use as in normal individuals. However, the protection that these vaccines afford may be either inadequate or transient, so that other infection control strategies should be simultaneously implemented.

ISSN:0312-5963    

出版商:ADIS    

年代:1992

数据来源: ADIS

摘要:

The widespread application of Bayesian parameter estimation in the area of therapeutic drug monitoring (TDM) has prompted the need for well conducted population studies to obtain relevant prior pharmacokinetic parameter estimates. In many cases the population has consisted of a relatively small number of subjects. This may be unavoidable for drugs used in cancer chemotherapy or in small, specific populations of patients. In contrast, information about drugs which are used extensively, such as the aminoglycosides, can be obtained by population studies which involve a large number of individuals. Indeed, this technique has proved particularly useful for determining parameter estimates which can be employed in neonatal TDM.Bayesian parameter estimation has been most frequently used for drugs with narrow therapeutic ranges such as the aminoglycosides, cyclosporin, digoxin, anticonvulsants (especially phenytoin), lithium and theophylline. However, the technique has now been extended to cytotoxic drugs, Factor VIII and warfarin. Bayesian methods have also been used to limit the number of samples required in more conventional pharmacokinetic studies with new drugs. Further advances in the use of these methods are likely to include measures of drug response and toxicity requiring population studies which also include relevant pharmacodynamic information.

ISSN:0312-5963    

出版商:ADIS    

年代:1992

数据来源: ADIS

摘要:

Quinidine pharmacokinetic behaviour was evaluated in 139 adult hospitalised men receiving oral quinidine therapy. A total of 391 serum quinidine concentrations were measured by enzyme immunoassay for routine clinical purposes. The NONMEM programme was used to examine the relationship between quinidine pharmacokinetics and several potential covariates. A 1-compartment open model with first-order absorption and elimination was assumed. The mean apparent volume of distribution (Vd) was about 230L. When measured,&agr;1-acid glycoprotein (AAG) levels were not included in the analysis. Oral quinidine clearance (CL) decreased with age, severe congestive heart failure and renal disease, and increased in patients with a history of alcohol abuse. The interpatient variability in CL and the intrapatient residual variability expressed as coefficients of variation (CV) were 28 and 31%, respectively. When AAG values were incorporated into the analysis, the only important covariates of CL were the AAG measurements and the presence of renal dysfunction as indicated by a calculated creatinine clearance of less than 50 ml/min (3 L/h). The interpatient variability in CL and the residual intrapatient CVs decreased to approximately 24 and 26%, respectively. Improvement of the CL model by inclusion of measured AAG strongly suggests that quinidine elimination is dependent on the free concentration of drug in plasma and supports the use of free serum quinidine concentrations when evaluating and monitoring quinidine therapy.

ISSN:0312-5963    

出版商:ADIS    

年代:1992

数据来源: ADIS

摘要:

A morbidly obese woman [190kg total bodyweight (TBW)] was admitted to hospital with a rapidly progressing wound infection. Over the next 2 weeks the patient developed congestive heart failure, acute renal failure, septic shock and multiple seizure episodes. Intravenous phenobarbital was added to phenytoin therapy to achieve seizure control. A total loading dose of phenobarbital 3700mg (19.5 mg/kg TBW) was administered in 3 divided doses. The initial dose of 1100mg resulted in a serum phenobarbital concentration of 6.3 mg/L 5h postinfusion, a second 1100mg dose increased the concentration to 13.1 mg/L 1h postinfusion and a final dose of 1500mg resulted in a 22.5 mg/L concentration at the end of the infusion. A phenobartital maintenance regimen of 120mg every 12h was then started. Peak serum concentrations of 19.8 and 17.8 mg/L were measured. All of the available serum phenobarbital concentrations and dosage amounts were fitted with least-squares nonlinear regression analysis to a 1-compartment model. An apparent volume of distribution (Vd) of 154.9L (0.82 L/kg TBW), total body clearance (CL) of 29 ml/min (1.74 L/h) and elimination half-life of 61h were determined.Our case report suggests that the dose of intravenous phenobarbital should be calculated using TBW. Additional studies are needed to precisely define the appropriate dosage weight, serum concentrations and clinical efficacy associated with intravenous phenobarbital in morbidly obese patients.

ISSN:0312-5963    

出版商:ADIS    

年代:1992

数据来源: ADIS