摘要:

Summary:An aminoglycoside Bayesian forecaster was evaluated in obese patients. This study assessed the influence of replacing the program‐supplied general population parameters (GPP) with obese population parameters (OPP) determined from the study population (n = 26). After entering the required patient information and the first peak and trough levels, patient‐specific pharmacokinetic parameters were generated by the Bayesian program based on GPP. These parameters were used to predict peak and trough levels for a second dosage regimen. Next, average OPP determined from a study population were substituted for the GPP, and the peak and trough levels were predicted again. Finally, Bayesian predictions of peak and trough levels were made in a validation population (n = 10), first with GPP, then with OPP. The accuracy of the predictions were evaluated through a prediction error analysis in which mean error indicates bias and mean absolute error and root meansquared error indicate precision. Means were statistically compared through a Student'sttest, with the significance level set at p < 0.05. For the study and validation populations, peak level predictions based on the OPP had less bias and greater precision than those predicted with GPP. Peaks predicted with GPP were statistically different from the observed peaks as well as the peaks predicted using the OPP. There was no statistical difference between the observed peaks and the predicted peaks using the OPP. The trough level predictions using GPP in the study population had less bias than those predicted using OPP; however, the OPP predictions had less bias in the validation population. Precision was similar for trough levels predicted by GPP and OPP. There was no statistical difference between the observed troughs and either of the predicted troughs. This study suggests that the Bayesian forecaster can provide better predictions in obese patients by changing the internal pharmacokinetic parameters from the GPP to the OPP.

ISSN:0163-4356    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

Summary:A computer program for phenytoin (PHT) dosing was developed containing seven different menus: two for drug‐naive patients, one using an empirical equation, the other using means forVmaxandKm; two for patients in whom either one or two dose rates and steady‐state concentrations are available; two for patients with hypoalbuminemia, and uremia, respectively; and one menu that optimizesVmaxandKmfrom available steady‐state concentrations. The program accepts or converts PHT and sodium PHT, and makes blood level correction for the concomitant administration of 25 different drugs. The evaluation of the program was done by retrospective analysis using data from three study pools: group I involved 47 patients from the University Hospital, group II relied upon 29 patient data supplied from a collaborative Veterans Administration study, and group III involved 26 patients from the Children's Hospital. Predictions were made and compared with found data to be within a range of ± 15, 20, or 25%. For study group III, many individual blood samples were <8 μg ml−1; hence, saturation kinetics may not have been involved. It is suspected that saturation kinetics in infants may begin at higher levels. Compliance seems to still be a major problem in PHT monitoring and dosage regimen adjustment. Accepting the data as they are, using one or two dose rates with the corresponding blood concentrations resulted overall in 73‐86% achieving blood levels within ± 25% of the predicted value.

ISSN:0163-4356    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

Summary:The absolute and relative predictive performances of one‐ and two‐compartment Bayesian forecasting models were evaluated and compared. Initial population parameters were derived from 25 adult patients with stable renal function and who were being treated for presumed or documented gram‐positive infections. The performance of each model was compared using these population parameters with and without steady‐state or non‐steady‐state feed‐back concentrations to predict future peak and trough concentrations in an additional 20 patients. Both models tended to underpredict vancomycin peak and trough concentrations obtained at steady state. The use of a two‐compartment model resulted in statistically less bias and more precise predictions of vancomycin peak concentrations when either population parameters or non‐steady‐state concentrations were used for future predictions. No difference in model performance was observed when steady‐state concentrations were used to predict future steady‐state concentrations. The results of this evaluation demonstrate that the two‐compartment Bayesian model is less biased and more precise in determining future vancomycin serum concentrations given only population parameters or non‐steady‐state feedback information. No difference in model performance could be discerned when steady‐state concentrations were used as feedback information.

ISSN:0163-4356    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

Summary:Michaelis‐Menten saturable pharmacokinetics confound the determination of appropriate phenytoin maintenance doses. This study retrospectively evaluated the performance of an IBM‐PC/XT computer program applying Bayesian regression to the “explicit solution to the Michaelis‐Menten equation.” Zero to five non‐steady‐state phenytoin serum concentrations were used to predict either non‐steady‐state concentrations at least 10 days in the future (n = 49) or steady‐state concentrations (n = 20). Non‐steady‐state concentration prediction precision (% mean absolute error) using 0‐5 non‐steady‐state feedbacks was 137%, 62%, 39%, 31%, 25%, and 15%, respectively, and steady‐state concentration prediction precision was 446%, 47%, 50%, 44%, 21%, and 13%, respectively. Elimination of subjects receiving concurrent drugs known to induce phenytoin metabolism significantly improved predictions based on population priors; however, performance improvements were not apparent after two serum level feedbacks. The program provided clinically acceptable predictions with four or more feedbacks. Refinement of population parameters and optimal sampling times should further improve performance.

ISSN:0163-4356    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

Summary:A high‐performance liquid chromatography method for the analysis of deferoxamine (DFO) in 100 &mgr;l of serum or plasma is described. The procedure involves the addition of the internal standard ciprofloxacin to the sample, followed by ultrafiltration to remove protein. The ultrafiltrate is then directly injected into the chromatography system. Separation is achieved using a reverse‐phase &mgr;Bondapak C18 column and a ternary solvent system (sodium phosphate:acetonitrile:methanol) running at 2.0 ml/min. Assay time is 10 min, and chromatograms show no interference from coadministered drugs during this period of time. Coefficients of variation were found to be less than 5%, and analytical recovery of DFO was 85%. Validation experiments in an experimental dog model and in patients with iron overload demonstrate that the method is appropriate for studying the pharmacokinetics of DFO in thalassemic patients receiving drug for the treatment of chronic iron overload.

ISSN:0163-4356    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

Summary:A noninstrumented enzyme immunochromatography (EIC) method for monitoring carbamazepine using whole blood was compared to the enzymemultiplied immunoassay technique (EMIT), fluorescence polarization immunoassay (FPIA), and high‐performance liquid chromatography (HPLC). Samples from 74 patients were evaluated in the comparison study, yielding correlation coefficients of 0.961 (EMIT), 0.974 (FPIA), and 0.867 (HPLC). The EIC method produced within‐run coefficients of variation of 4.3%, 4.9%, and 5.8% for three carbamazepine concentrations. The between‐run coefficient of variation over 107 days was 4.9%. The spiked serum sample analysis yielded recovery rates ranging from 98 to 102%. Enzyme immunochromatography was found to be a useful noninstrumented method for on‐site testing. The test gives quantitative patient sample results comparable to the results obtained using established laboratory methods.

ISSN:0163-4356    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

Summary:A comparison of the precision and accuracy of three nonisotopic and of radioimmunoassay (RIA) techniques for digoxin was made using data from 141 samples of spiked human serum assayed between 1984 and 1987 by members of the Heathcontrol external quality assurance scheme. There were significant differences between techniques in the number of observations rejected as outliers greater than 3 SD from the sample mean, the percentages of rejected measurements being Abbott TDX 1.4, RIA 3.3, Ames TDA 4.2, and Syva EMIT 6.3. Ames TDA and Syva EMIT were shown to have a significantly lower precision than the other techniques in measurements of digoxin concentrations <1 nmol/L. A significant 4% negative bias was observed for Ames TDA measurements of digoxin concentrations between 1 and 2.6 nmol/L. A concentration‐related bias was demonstrated for Abbott TDX measurements that varied from 14% overestimates at concentrations <1 nmol/L to 6.7% underestimates of digoxin at concentrations >2.6 nmol/L.

ISSN:0163-4356    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

Summary:The new Abbott TDx cyclosporine and metabolites fluorescent polarization immunoassay procedure provides a 20‐min sample turn‐around time, using 50 &mgr;l of sample for the analysis of cyclosporine in whole blood. A precipitation agent and a lysing agent are utilized as a pretreatment step. The range of the whole blood assay is from 0 to 2,000 ng/ml, with a sensitivity of 50 ng/ml. Precision studies at 3 control levels provided coefficients of variation of 2.1‐4.8% for both assays. In order to compare this assay with the currently used Sandoz polyclonal radioimmunoassay (RIA) method, 200 whole blood samples were obtained from 20 renal, cardiac, and hepatic transplant recipients. The mean whole blood cyclosporine concentrations for samples above the sensitivity level were as follows: TDx 754 ng/ml (±31) andRIA619 ng/ml (±22). Blood TDx levels correlated strongly with RIA levels, with a regression coefficient ofr= 0.915. This new assay provides reliable blood cyclosporine concentrations that correlate well with RIA measurements. This assay offers rapid sample turn‐around times, making same‐day results for outpatient drug monitoring possible.

ISSN:0163-4356    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

Summary:Rat cerebral cortex was used to prepare a suspension of benzodiazepine receptors. The suspension was mixed with an extract of specimen and [3H]flunitrazepam. The mixture was filtered through a membrane, and radioactivity on the membrane was measured. Clonazepam concentrations in patient plasma specimens determined by radioreceptor assay and gas‐liquid chromatography agreed well. However, diazepam equivalent concentrations determined by radioreceptor assay were close to the sum of diazepam and desmethyldiazepam concentrations determined by high‐performance liquid chromatography, as desmethyldiazepam had binding activity for the receptor. This receptor assay method is accurate, simple, requires less than 0.5 ml of plasma, and is therefore suitable for analyzing numerous samples in a short time.

ISSN:0163-4356    

出版商:OVID    

年代:1989

数据来源: OVID

ISSN:0163-4356    

出版商:OVID    

年代:1989

数据来源: OVID