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1. |
Editorial |
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Therapeutic Drug Monitoring,
Volume 12,
Issue 1,
1990,
Page 1-1
C. Pippenger,
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ISSN:0163-4356
出版商:OVID
年代:1990
数据来源: OVID
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2. |
Onset and Development of Cyclosporin A Effects on Lymphocytes of Cardiac Patients Before Heart Transplantation |
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Therapeutic Drug Monitoring,
Volume 12,
Issue 1,
1990,
Page 2-7
E. Albengres,
P. Riant,
M. Morel,
C. Hamberger,
O. Tavolaro,
D. Loisance,
J. Tillement,
J. Cachera,
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摘要:
The effects of cyclosporin A (CSA) in low dosage (4 mg/kg/24 h i.v.) were studied in 17 patients awaiting heart transplantation. The lymphocyte subsets were typed, enumerated, and their proliferation measured before CSA perfusion, after infusion (over 24 h), and then again after two further 24 h intervals (To h,T24 h,T48h, andT72 h). No significant change was found in T or B enumerations although lymphocyte function was markedly modified. For all 17 patients, there was a significant decrease in lymphocyte proliferation that was, however, re-established after 72 h for 14 of the patients, but not for the remaining 3. Inhibition of the proliferative response was found to occur rapidly, to be potent although rapidly reversible in most cases, while yet subject to wide interindividual variability. These four features suggest that (a) CSA in fixed doses may alter the balance between helper and suppressor cells in varying degrees according to the patient, and that (b) CSA given immediately or shortly after heart transplantation could be beneficial.
ISSN:0163-4356
出版商:OVID
年代:1990
数据来源: OVID
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3. |
Area‐Under‐the‐Curve Monitoring of Cyclosporine TherapyPerformance of Different Assay Methods and Their Target Concentrations |
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Therapeutic Drug Monitoring,
Volume 12,
Issue 1,
1990,
Page 8-15
J. Grevel,
K. Napoli,
S. Gibbons,
B. Kahan,
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摘要:
The measurement of areas under the concentration-time curve (AUC) was recently introduced as an alternative to trough level monitoring of cyclosporine therapy. The AUC is divided by the oral dosing interval to calculate an average concentration. All measurements are performed at clinical steady state. The initial evaluation of AUC monitoring showed advantages over trough level monitoring with concentrations of cyclosporine measured in serum by the polyclonal radioimmunoassay of Sandoz. This assay technique is no longer available and the following assays were performed in parallel during up to 173 AUC determinations in 51 consecutive renal transplant patients: polyclonal fluorescence polarization immunoassay of Abbott in serum, specific and nonspecific monoclonal radioimmunoassays using3H and125I tracers in serum and whole blood, and high performance liquid chromatography in whole blood. Both trough levels and average concentrations at steady state measured by those different techniques were significantly correlated with the oral dose. The best correlation (r2= 0.54) was shown by average concentrations measured in whole blood by the specific monoclonal radioimmunoassay of Sandoz (3H tracer). This monitoring technique was also associated with the smallest absolute error between repeated observations in the same patient while the oral dose rate remained the same or was changed. Both allegedly specific monoclonal radioimmunoassays (with3H and125I tracer) measured significantly higher concentrations than the liquid chromatography. The following target values for average steady state concentrations were calculated based on correlations of the new methods with the polyclonal radioimmunoassay in serum, for which a target of 200 ng/ml had been established: specific monoclonal radioimmunoassay in serum, 144 ng/ml; nonspecific monoclonal radioimmunoassay in serum, 331 ng/ml; fluorescence polarization immunoassay in serum, 233 ng/ml; liquid chromatography in whole blood, 272 ng/ml; specific monoclonal radioimmunoassay with3H tracer in whole blood, 372 ng/ml; and specific monoclonal radioimmunoassay with125I tracer in whole blood, 431 ng/ml.
ISSN:0163-4356
出版商:OVID
年代:1990
数据来源: OVID
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4. |
Bayesian Estimation of Cyclosporine Clearance in Bone Marrow Graft |
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Therapeutic Drug Monitoring,
Volume 12,
Issue 1,
1990,
Page 16-22
F. Serre-Debeauvais,
A. Iliadis,
B. Tranchand,
M. Michallet,
S. Benzekri,
C. Ardiet,
J. Cano,
M. Hollard,
M. Gavend,
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摘要:
The dosage regimen of cyclosporine (CsA) can be individualized in patients by means of a test dose (TD) method in the few days before bone marrow graft. To simplify the test dosing protocol, we used a Bayesian estimation (BE) of CsA clearance requiring population data and partial kinetic information for a given patient. In the first part, 42 patients, aged 11–47 years, were given a 2-h infusion of CsA (4 mg · kg-1). CsA concentrations were determined in several blood samples. The obtained concentration-time curves were fitted according to a three-compartment model. Maximum likelihood estimation (MLE) allowed CsA determination of pharmacokinetic parameters. Early population parameters of CsA were determined using 22 TD by a two-stage method. In the remaining 20 patients, individual pharmacokinetic parameters were also computed by BE procedure, taking into account the above determined population parameters and CsA concentration determinations from three blood samples drawn at 5 and 30 min and 3 h after the end of TD infusion. In the second part, 16 patients were used to evaluate performance of BE in directly predicting target concentration values. Finally, early population characteristics were updated on the basis of 42 patients. Statistical comparisons between MLE and BE estimates of CsA clearance and between concentrations predicted after BE and those experimentally obtained showed that three blood CsA determinations allowed accurate clearance estimation and target concentration predictions. The method presented here can be used to calculate an individual CsA dosage regimen in real time, thus improving patient comfort. Furthermore, this real-time dosage regimen adjustment is more suitable, as it makes it possible to avoid the dependence phenomena of CsA kinetics over a long time period.
ISSN:0163-4356
出版商:OVID
年代:1990
数据来源: OVID
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5. |
Antiarrhythmic Activity and Unbound Concentrations of Disopyramide Enantiomers in Patients |
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Therapeutic Drug Monitoring,
Volume 12,
Issue 1,
1990,
Page 23-28
John Lima,
Stephen Wenzke,
Harisios Boudoulas,
Stephen Schaal,
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摘要:
Six patients with reproducible inducible atrial flutter randomly received, in double-blinded fashion, 77 mg of S( + )-disopyramide and R( – )-disopyramide over 20 min by intravenous infusion on two occasions separated by at least 24 h. The S( + ) enantiomer prevented the inducibility of atrial flutter in five of the six patients; atrial flutter was inducible following R( – ) enantiomer administration in all six patients (p < 0.05). The mean (±SD) antiarrhythmic unbound serum concentration range of S( + )-disopyramide was 0.55 ± 0.31–0.90 ± 0.81 mg/L. The binding of disopyramide was stereoselective: the mean unbound fractions of S( + )- and R( – )-disopyramide were 0.207 ± 0.119 and 0.338 ± 0.214 (p < 0.05). Binding of the individual enantiomers in some patients was markedly concentration dependent. The data suggest that the antiarrhythmic activity associated with racemic disopyramide resides in the S( + ) enantiomer.
ISSN:0163-4356
出版商:OVID
年代:1990
数据来源: OVID
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6. |
Pharmacokinetics of Intravenous Vancomycin in Patients with End‐Stage Renal Failure |
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Therapeutic Drug Monitoring,
Volume 12,
Issue 1,
1990,
Page 29-34
C. Tan,
H. Lee,
T. Ti,
E. Lee,
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摘要:
The pharmacokinetics of a 500-mg dose of i.v. vancomycin were studied in six Chinese patients with end-stage renal failure. Serum vancomycin concentrations were determined by high-performance liquid chromatography. Observed peak and trough (at 168 h postinfusion) concentrations were in the range of 14.2–35.0 μg/ml and 2.8–5.5 μg/ml, respectively. The data were analyzed using the PCNONLIN. In all six patients, the data could be fitted well by both the biexponential and triexponential models, but in three patients the latter model provided a better fit. Two-compartment pharmacokinetic parameters obtained from the six patients weret1/2α 1.13 ± 0.25 h (mean ± SEM),t1/2β 121.3 ± 8.2 h,Vc0.45 ± 0.09 L/kg, Vss 1.00 ± 0.12 L/kg,ClT5.90 ± 0.69 ml/kg/h, and the calculatedCmax25.0 ± 6.1 μg/ml. The mean vancomycin serum protein binding was 18.5 ± 12.0% as compared with a mean of 46.0% in pooled serum from normal controls. Hemodialysis had no significant effect on vancomycin protein binding or clearance. On the basis of our kinetic study, 500 mg of vancomycin given every seven days is probably adequate treatment for methicillin resistantStaphylococcus aureusinfection in end-stage renal failure patients, but further clinical studies are necessary to confirm this.
ISSN:0163-4356
出版商:OVID
年代:1990
数据来源: OVID
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7. |
Validity of a Two‐Point Acetaminophen Pharmacokinetic Study |
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Therapeutic Drug Monitoring,
Volume 12,
Issue 1,
1990,
Page 35-39
Joseph Scavone,
David Greenblatt,
Gershwin Blyden,
Becki Luna,
Jerold Harmatz,
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摘要:
The pharmacokinetics of a single 650-mg intravenous dose of acetaminophen were determined in 82 volunteers using multiple (13 or more) plasma acetaminophen concentrations measured by high pressure liquid chromatography during 24 h after dosage. Kinetic values from the complete study were compared with kinetic estimates based on only two data points: (a) the 2-and 6-h points only; and (b) the 3 and 6-h points only. For elimination half-life, values from the complete study (mean 2.42 h) were highly correlated (r= 0.87 and 0.84) with methods a and b (means 2.41 and 2.43 h), with regression slopes of 1.00 and 0.99, respectively. For clearance, the complete study values (mean 312 ml/min) were highly correlated (r= 0.97 and 0.97) with method a and b values, but both two-point methods significantly overestimated clearance (means 350 and 355 ml/min) by an average of 13 and 14%, respectively. Results for volume of distribution were similar to those for clearance. Although acetaminophen elimination half-life can be estimated with reasonable precision using a two-point blood-sampling procedure, clearance and volume of distribution values using the two-point method overestimate the actual values.
ISSN:0163-4356
出版商:OVID
年代:1990
数据来源: OVID
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8. |
Protein Binding of Antiepileptic Drugs During Pregnancy, Labor, and Puerperium |
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Therapeutic Drug Monitoring,
Volume 12,
Issue 1,
1990,
Page 40-46
A. Bardy,
V. Hiilesmaa,
K. Teramo,
P. Neuvonen,
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摘要:
Twenty-four epileptic women were followed-up during late pregnancy, labor, and early puerperium in order to detect possible alterations in serum protein binding of antiepileptic drugs (AEDs). The total and free concentrations of carbamazepine (CBZ), phenytoin (PHT), and valproate (VPA) in maternal serum were measured. In addition, the concentrations of albumin, α1-acid glycoprotein (AGP), and free fatty acids (FFA) were also measured. Total AED concentrations during labor were influenced by changes in drug dosages; total PHT increased during the first puerperal weeks. During labor the free fraction of CBZ remained stable, whereas PHT and particularly VPA free fractions increased. This phenomenon was parallel to the increase in FFA concentration; FFA concentrations decreased again during the first days post-partum. Albumin and AGP concentrations were low during pregnancy and labor, and increased after delivery. The total umbilical CBZ and PHT concentrations were not significantly different from maternal concentrations. The total VPA concentration in umbilical serum was significantly higher than that in maternal serum. The free fraction of CBZ was higher and that of PHT and VPA lower in umbilical than in maternal serum at delivery. Umbilical cord serum had a higher albumin but a lower AGP and FFA concentration than maternal serum. The changes in PHT and particularly VPA free fraction associated with changes in FFA concentration should be considered when assessing the total concentration of these drugs in maternal and umbilical serum.
ISSN:0163-4356
出版商:OVID
年代:1990
数据来源: OVID
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9. |
An Evaluation of Bayesian Microcomputer Predictions of Theophylline Concentrations in Newborn Infants |
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Therapeutic Drug Monitoring,
Volume 12,
Issue 1,
1990,
Page 47-53
M. Murphy,
Carl Peck,
Gerald Merenstein,
Donna Rodden,
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摘要:
Determination of appropriate theophylline maintenance doses in preterm infants is confounded by interpatient variability. This study evaluated the performance of an IBM PC computer program applying Bayesian regression before and during steady state in 37 preterm infants. Prior population estimates of clearance and distribution volume in preterm infants and Bayesian estimates of clearance and distribution volume based on one to three theophylline plasma concentrations were used to predict subsequent concentrations (drawn 1–17 days later). We assessed the accuracy and precision of the predictive performance of the Bayesian program with the mean prediction error and the mean absolute prediction error. The absolute prediction error (mean absolute error ± SEM) significantly decreased with increasing feedback concentrations from 3.54 ± 0.45 μg/ml (population estimates) to 2.74 ± 0.42 (one feedback) and 2.02 ± 0.35 μg/ml (two feedback concentrations). Mean prediction errors (±SEM) based on one to three feedbacks (-1.5 ± 0.40 μ/ml) were significant improvements over population predictions (- 2.63 ± 0.72 μ/ml,p< 0.05), although a small but significant average overprediction remained. Absolute prediction error was correlated with postconceptional and postnatal age when zero or one but not two feedback concentrations were available. Computer program predictions based on one measured feedback concentration were more accurate and precise than population-based predictions. Refinement of population parameters or two feedback concentrations further improved performance.
ISSN:0163-4356
出版商:OVID
年代:1990
数据来源: OVID
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10. |
Theophylline Pharmacokinetics in Black Zimbabwean Males |
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Therapeutic Drug Monitoring,
Volume 12,
Issue 1,
1990,
Page 54-58
John Jameson,
Agatha Munyika,
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摘要:
Theophylline pharmacokinetics were studied in 16 black Zimbabwean volunteers aged 20–41 years. Following a single intravenous dose of 5 mg/kg, four serum levels were collected over 24 h. Data were analyzed using a one-compartment open model. The correlation coefficient was 0.995 ± 0.004. The mean extrapolated peak level was 8.5 ± 0.9 mg/L. The mean half-life and volume of distribution were 10.1 ± 3.1 h and 0.55 ± 0.7 L/kg, respectively. The mean clearance was 0.62 ± 0.17 ml/kg/min. The mean weight was 7 kg less than the calculated ideal body weight. These data suggest a larger volume of distribution and longer half-life than in other reported populations. The clearance is on the low end of previously reported values. We postulate that the primary cause of the large volume is the decreased body fat and consequent increase in body water per kilogram. The slightly decreased clearance may have been partially due to the high carbohydrate, low protein diet of our subjects. The long half-life is simply a reflection of a large volume and a moderately low clearance. We suggest that standard per kilogram maintenance doses can be employed in this population. A larger loading dose of 8 mg/kg aminophylline is recommended. Finally, the lack of sustained release theophylline in Zimbabwe may not be a problem, given the longer half lives observed in this study.
ISSN:0163-4356
出版商:OVID
年代:1990
数据来源: OVID
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