摘要:

For many drugs, therapeutic drug monitoring (TDM) has become widely available and accepted as an important component of clinical decision making in the intensive care nursery setting. This review analyzes the potential factors that can either expand or restrict neonatal TDM. A case is made for the development of pharmacokinetic services designed to meet the needs of sick neonates. These patients are well known for their extreme physiological instability, often resulting in drug concentrations obtained in non-steady-state conditions. Potential for toxic effects is also increased in this population. Appropriate collection and interpretation of measured concentrations is critical. The future of neonatal TDM is linked to that of TDM services in general. High cost, expensive technology, and ethical and political factors, however, set apart the population of very low birth weight infants from the universe of patients receiving TDM services.

ISSN:0163-4356    

出版商:OVID    

年代:1990

数据来源: OVID

摘要:

Although calcium channel blockers have been reported to increase trough cyclosporine (CsA) blood levels, few studies have systematically examined the effects of calcium channel blockers on CsA pharmacokinetics. In the present investigation, complete pharmacokinetic profiles of CsA and its major metabolites (Ml, M17, and M21) were determined in 11 verapamil treated patients, 7 nifedipine-treated patients, and in 78 controls. Whole blood and urine levels were analyzed using high-performance liquid chromatography. Verapamil caused a 45% increase in CsA area under the curve, maximum concentration, steady-state concentration, and trough level. Metabolite 17 levels were increased in a parallel fashion, suggesting that altered CsA bioavail ability rather than decreased metabolism may have caused the higher CsA levels in verapamil-treated patients. However, verapmil-induced reductions in CsA metabolism by other routes could not be ruled out. No changes in CsA or its metabolites were observed in nifedipine-treated patients. Unlike previous reports in patients treated with higher CsA doses, verapamil and nifedipine did not improve renal function in the present study. Nevertheless, the increase in CsA blood levels seen with verapamil may enhance the therapeutic cost-effectiveness of this agent in hypertensive renal transplant recipients.

ISSN:0163-4356    

出版商:OVID    

年代:1990

数据来源: OVID

摘要:

This study was performed to determine the effect of omeprazole, given in therapeutically recommended doses, on the steady-state plasma levels of phenytoin in epileptic patients. Five men and three women of median age 34 years participated in the study. Steady-state plasma levels of phenytoin were measured once a week for 2 weeks before and after, respectively, and during 3 weeks of concomitant omeprazole treatment with 20 mg daily. Urinary excretion of phenytoin and its metabolite [5-(p-hydroxyphenyl)-5-phenyl-hydantoin were determined before and at the end of the omeprazole treatment period. The steady-state plasma phenytoin levels as well as urinary excretion of phenytoin and its main metabolite were unchanged during omeprazole treatment. The results from this study suggest that concomitant omeprazole treatment in therapeutically recommended doses (20 mg daily) will not significantly affect the steady-state plasma levels of phenytoin in epileptic patients.

ISSN:0163-4356    

出版商:OVID    

年代:1990

数据来源: OVID

摘要:

Two factors have limited the use of saliva in monitoring phenytoin therapy: availability of adequate volume of clear saliva and lack of a sensitive phenytoin assay. The applicability of citric acid-stimulated saliva and of a sensitive analytical assay (fluorescence polarization immunoassay, “TDx” Abbott) was evaluated in this study. Phenytoin was measured in paired plasma-saliva specimens from epileptic children during the long-term or the initial phase of phenytoin therapy. Analysis was carried out in plasma and in the clear supernatant of saliva (following centrifugation). Pooled-estimate SD of the analytical assay variability was 0.175 μg/ml for plasma total phenytoin, 0.063 for plasma free phenytoin, and 0.009 for saliva phenytoin. Recovery measurements of phenytoin spiked into saliva samples gave a coefficient of variation of less than 5%. Correlations between saliva and total plasma phenytoin levels and between saliva and free plasma phenytoin levels were strong and highly significant (r = 0.99,p< 0.01). The percentage of temporal fluctuation (as determined by saliva phenytoin profiles) during 10–24 h ranged between 25.5–177 (mean, 58.3; SD, 47.3). Ratios of plasma total phenytoin/saliva phenytoin and of plasma free phenytoin/saliva phenytoin levels were 9.54 ± 1.05 and 0.71 ± 0.09, respectively. Dialysis experiments showed no binding of phenytoin to saliva supernatant. The greater saliva phenytoin concentrations as compared to plasma free phenytoin concentrations could be due to active transport of phenytoin from plasma to saliva. Measurement of phenytoin in citric acid-stimulated saliva by fluorescent polarization immunoassay is a reliable, noninvasive, and convenient method for monitoring phenytoin therapy in children.

ISSN:0163-4356    

出版商:OVID    

年代:1990

数据来源: OVID

摘要:

Two specific high-performance liquid chromatography methods for determining plasma concentrations of azathioprine and 6 mercaptopurine after oral administration of azathioprine are presented. It was shown that azathioprine is unstable in the blood samples unless immediately cooled in ice water. The 2-amino analog, guaneran, was used as internal standard for azathioprine, which was extracted from plasma with ethylacetate. A Nucleosil C18 column was used for the separation. The detection limit was 6 nM. For quantification of 6-mercaptopurine, 6-thioguanine was used as internal standard. Plasma was deproteinized with HC104and the sample was purified on mercurial cellulose. A Beckman ODS column was used and the detection limit was 5 nM. Phar-macokinetic data from two patients are presented. Unchanged azathioprine was seen until 6 h after an oral dose of 32 mg/m2.

ISSN:0163-4356    

出版商:OVID    

年代:1990

数据来源: OVID

摘要:

Cyclosporine (CsA) concentrations were prospectively monitored for 6 months after transplantation in 66 consecutive renal transplant recipients. Analysis for CsA was performed with polyclonal radioimmunoassay (RIA), high-performance liquid chromatography (HPLC), and fluorescence polarization immunoassay (FPIA) in whole blood and plasma, and with specific and nonspecific monoclonal RIA in whole blood. Precision within and between runs was best with FPIA, followed by HPLC and RIA. A strong correlation was observed between the results obtained with HPLC and specific monoclonal RIA (r= 0.98). Correlation coefficients between the other assays ranged from 0.56 (plasma HPLC versus blood polyclonal RIA) to 0.91 (blood nonspecific monoclonal RIA versus blood FPIA). The highest values for CsA concentrations in blood were found with nonspecific monoclonal RIA, followed by FPIA and polyclonal RIA (mean ratio versus specific monoclonal RIA was 3.3, 2.9, and 2.4, respectively). Specific monoclonal RIA had 7% higher values than HPLC. There was a more than threefold interindividual variation in the mean ratio between specifically and nonspecifically measured CsA concentrations in whole blood and plasma. The ratio between CsA concentrations, determined with specific versus nonspecific methods in whole blood, decreased significantly during the first month after transplantation (from 0.42 to 0.35, as assayed with specific monoclonal RIA versus polyclonal RIA in whole blood;p< 0.05). The concentrations in blood were, on the average, three times higher than those in plasma, although there was a more than fourfold interindividual variation in the mean values. The large interindividual variations in ratios between the results obtained in different assays and in different media show that each procedure for monitoring of CsA in transplant patients has to be evaluated separately. Moreover, specific analytical methods should be used for monitoring CsA.

ISSN:0163-4356    

出版商:OVID    

年代:1990

数据来源: OVID

摘要:

We have determined blood cyclosporine concentrations using three different methods in a total of 212 therapeutic monitoring specimens from heart, liver, kidney, and bone marrow transplant recipients. The specimens were analyzed by radioimmunoassay using a polyclonal nonspecific antibody (RIA, Ciclosporin RIA-Kit), radioimmunoassay using a monoclonal specific antibody (SRIA, Sandimmun Kit), and by high-performance liquid chromatography (HPLC). When the nonspecific antibody was used, mean RIA/HPLC ratios in different patient groups ranged from 2.3 to 5.5, and the variability in this ratio was large in all groups. When the specific antibody was used, mean SRIA/HPLC ratios in different groups ranged from 1.1 to 1.5, with smaller variability. It can be concluded that radioimmunoassay using a specific monoclonal antibody is well suited for therapeutic monitoring of blood cyclosporine concentrations. However, even this method overestimates cyclosporine concentrations in certain patients.

ISSN:0163-4356    

出版商:OVID    

年代:1990

数据来源: OVID

摘要:

This study evaluated a new, simple, disposable visual measuring device (AccuLevel), which uses enzyme immunochromatography to indicate visually, without any instrument, the concentrations of three major antiepileptic drugs (AEDs) in small blood samples. Drug levels (30 values for diphenyl-hydantoin, 41 for phenobarbital, and 40 for carbamazepine) obtained by AccuLevel were compared with those obtained with the enzyme-multiplied immunoassay technique (EMIT). Results showed an excellent correlation between EMIT and AccuLevel data for the three major AEDs. The method appears to be particularly suitable in outpatients and in case of emergency.

ISSN:0163-4356    

出版商:OVID    

年代:1990

数据来源: OVID

摘要:

The analysis of pentamidine in whole blood, plasma, and urine by liquid chromatography is described. Extraction was made with a mixture of acetonitrile and chloroform followed by back-extraction into phosphate buffer. A reversed-phase chromatographic system with fluorescence detection was used. The precision of the method was 5–7% at the lower limit of determination (16 nmol/L in plasma and hemolyzed whole blood, 27.7 nmol/L in urine).

ISSN:0163-4356    

出版商:OVID    

年代:1990

数据来源: OVID

摘要:

We have evaluated three quantitative colorimetric methods [bromthymol blue (BTB), Haskins, and Saker-Salomons (S-S) for measurement of concentrations of chloroquine (CQ) in urine. A graphical evaluation of test sensitivity and test specificity at different concentrations of CQ in authentic urine samples was used. Liquid chromatography (LC) was used as a reference method. The Haskins method showed the highest test specificity (89%) and test sensitivity (97%), at a discrimination value of 2 μmol/L. At the same sensitivity (97%) as the Haskins method, S-S and BTB methods had test specificities of 49 and 13%, respectively. The correlation coefficients between the LC method and the colorimetric methods were all higher than 0.94 at a urinary concentration range of 2–100 μmol/L. The intra- and interassay variations for the colorimetric methods were all uniformly

ISSN:0163-4356    

出版商:OVID    

年代:1990

数据来源: OVID