ISSN:0163-4356    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

Fifteen patients were studied during short-term (5 days at 10–15 mg/m2/day) or long-term (5–104 days at 3 mg/m2/day) doxorubicin infusion. Levels of doxorubicin and metabolites in serum and 24-h timed urine collections were determined by high-performance liquid chromatography. Quantifiable anthracycline levels were identified in serum of 5 of 6 patients (6 courses) receiving drug at 10 mg/m2/day. In 5 courses, total anthracycline levels were 10–80 ng/ml, whereas levels as high as 370 ng/ml were observed in a patient with hepatorenal failure. No detectable serum levels of anthracycline were seen in patients receiving long-term doxorubicin therapy. Although analysis of 24-h timed urine collections revealed that doxorubicin was the predominant anthracycline, the extent of urinary elimination showed considerable interpatient variation (1.0–52.5% of the infused dose/24-h period on the short-term protocol and 5.3–57.2%/24-h period on the long-term protocol). Metabolic processing of doxorubicin administered by continuous infusion was found to be similar to that of drug given by bolus administration and showed no change in pattern with time. However, a greater variability in serum and urinary anthracycline levels was seen among patients on infusion schedules than has been noted with bolus drug treatment.

ISSN:0163-4356    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

The pharmacokinetic and pharmacodynamic interactions between digoxin and propafenone were investigated in 10 hospitalized patients with heart disease and cardiac arrhythmias. During steady state (0.25 mg/day) the glycoside was combined with 600 mg of propafenone daily for 1 week. The mean \pm SD serum digoxin concentration (SDC) was 0.97 \pm 0.29 ng/ml before and 1.54 \pm 0.65 ng/ml (p < 0.003) during propafenone administration. Propafenone induced a mean decrease in 31.1 and 31.7% in total and renal digoxin clearances, respectively. The increase in SDCs was accompanied by a decrease in heart rate (HR) and shortening of QTc(QT interval corrected for HR). In patients receiving digoxin and propafenone simultaneously, the SDCs should be monitored and the digoxin dose reduced if there is evidence of toxicity.

ISSN:0163-4356    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

We studied pharmacokinetic variables in 100 neonates to evaluate the need for a loading dose of gentamicin. The mean volume of distribution for gentamicin in this population was .542 \pm .205 L/kg. Forty-five percent of these patients would not achieve peak serum concentrations of 5 mUg/ml after one dose of 2.5 mg/kg. A loading dose of 4 mg/kg would result in a level of 5 mUg/ml in 92% of the patients. After this study, a 4 mg/kg loading dose was initiated at our institution. Peak and trough concentrations at steady state were compared in 50 patients receiving a loading dose and 40 patients who had not received a loading dose. No significant differences were found in peak or trough concentrations after three or more doses, verifying that a loading dose does not affect steady-state concentrations. Because gentamicin toxicities are related to accumulation over time, whereas therapeutic efficacy may be related to early attainment of therapeutic peak serum concentrations, we recommend a loading dose of 4 mg/kg in all neonates beginning gentamicin therapy.

ISSN:0163-4356    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

Fluctuations in the carbamazepine (CBZ) concentration during the day were studied using the profiles of 88 patients on slow release CBZ preparations. Blood was taken at 800, 1100,1400,1700, 2000, 2200 and 800 hr of the following day. The CBZ dosage was divided into two equal doses and administered at 800 and 2000 h. The influence of different factors on the fluctuations in the CBZ concentration during the day was studied. The fluctuation correlated negatively (r = −0.51, p < 0.001) with the level-dose ratio LDR (CBZ morning concentration-CBZ dose per body weight ratio). The co-medication and preparation had no additional significant influence on fluctuations in the CBZ concentration during the day. The maximal CBZ serum concentration during the day can be described for most patients as a function of the CBZ morning concentration and the level-dose ratio using a suitable regression equation (r = 0.93, standard error of estimate = 1.2 mg/L).

ISSN:0163-4356    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

The performance of the Bayesian feedback method for predicting lignocaine dosage developed by Vozeh et al. was evaluated in 53 Japanese patients, treated for either suppression or prophylaxis of ventricular arrhythmias, with respect to accuracy, precision, efficiency, and safety. The lignocaine serum concentrations at 12 h (C12) and 24 h (C24) after continuous infusion was started were predicted and compared retrospectively using the early concentration at 2–4 h (C2–4). The mean of the prediction error (PE) and the root mean-squared error (RMSE) were used as a measure of accuracy and precision. The 95% confidence interval of PE for C12included zero, but those of PE for C24, whether C2–4was used alone or in combination with C12, were less than zero, meaning that the prediction of C24was significantly biased. The RMSE for C12(13.2%) was less than that for C24(16.2%), but the difference was not statistically significant. The fraction of measurements lying within the statistically approximate 68% prediction interval (\pm 1 SD) was used to evaluate the estimate of the SD of prediction. The fraction of measurements inside the prediction interval was significantly larger than the expected 68% for both C12and C24(p < 0.05), showing that the estimate of the size of the PE is biased on the safer side. The clinical effects of lignocaine were also evaluated from the viewpoints of suppression of number of ventricular premature beats, prevention of more severe grades of arrhythmias, and toxicity. At least the appearance of toxicity, which four patients exhibited, was related to the lignocaine serum concentration (>6 mUg/ml).

ISSN:0163-4356    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

The current study was performed to document the cost savings and need for a therapeutic drug monitoring program for phenytoin. The methodology employed a prospective, randomized, crossover design that utilized two control and two therapeutic drug monitoring phases. The therapeutic drug monitoring program significantly decreased the average number of assays performed per patient from 2.14 to 0.61. Withdrawal of the program resulted in a significant increase in the average number of assays performed per patient (from 0.61 to 2.41), the average number of assays drawn incorrectly (from 0.39 to 1.89), and in the average number of assays used inappropriately (from 0.50 to 2.07). Withdrawal of the program was also associated with a significant increase in the average number of readmissions (from 0 to 0.19) within 3 months of discharge. Reinstitution of the program was associated with a significant decrease in the average number of readmissions (from 0.19 to 0.03) within 3 months of discharge. The cost savings from decreasing the number of assays performed was estimated to be 100.00 for the first year.

ISSN:0163-4356    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

We assessed the performance of a predictive algorithm for dosing aminoglycoside antibiotics in 75 pediatric patients and Bayesian feedback in 36. The absolute errors for peak and trough concentrations were 1.83 and 0.80 mUg/ml, respectively, which seem clinically acceptable for most patients. However, the algorithm had significant negative bias for both peaks and troughs. Implementation of Bayesian feedback eliminated bias in a second set of concentrations and significantly decreased its magnitude for both peaks (p= 0.028) and troughs (p= 0.005). This method may allow more accurate dosing of aminoglycoside antibiotics in pediatric patients, though it would most likely be improved by better definition of population parameters and their variability.

ISSN:0163-4356    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

The terms “serum concentration” and “plasma concentration” are often used interchangeably in therapeutic drug monitoring, but few studies have addressed the comparability of serum and plasma drug concentrations. Before implementing a change in the procedure for measuring aminoglycoside concentrations in our institution, we prospectively compared values for tobramycin and gentamicin concentrations measured in serum and plasma. For the 208 samples that were tested, plasma aminoglycoside concentrations were significantly lower than those in serum. This relationship was similar for to bramycin and gentamicin, and was unaffected by the presence of concurrent therapy with ticarcillin. This difference, while statistically significant, was not, in our estimation, of sufficient magnitude to be of clinical importance. Plasma aminoglycoside concentrations may be considered equivalent to serum concentrations and, owing to the shorter processing time involved, appear to be the preferred medium for measuring these values.

ISSN:0163-4356    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

To determine the effects of erythromycin on multiple-dose carbamazepine pharmacokinetics, seven healthy male volunteers were given 300–400 mg of carbamazepine each morning for 17 consecutive days. All subjects were given a placebo erythromycin form every 6 h on days 12, 13, and 14, then changed to erythromycin base 250 mg every 6 h for the final 3 days. Serial blood samples were drawn after the morning doses on days 14 and 17. Analysis of carbamazepine and carbamazepine-10,11-epoxide concentrations were made by high-performance liquid chromatography. Pharmacokinetic analysis showed carbamazepine half-life and 24-h postdose concentration to increase significantly (p < 0.05) and oral clearance to decrease (p < 0.05) during erythromycin administration. Decreases in carbamazepine-10,11-epoxideCmax(p< 0.001), area under the concentration-time curveo-24(p < 0.001), and carbamazepine-10,11-epoxide to carbamazepine ratio (p < 0.01) also occurred during carbamazepine dosing. Erythromycin significantly inhibits the epoxide-diol metabolic pathway by which carbamazepine is transformed to carbamazepine-10,11-epoxide. Wide individual variability in this interaction should serve to warn practitioners of the unpredictability of this interaction.

ISSN:0163-4356    

出版商:OVID    

年代:1989

数据来源: OVID