摘要:

Aminoglycosides have rightly remained a cost-effective anti-microbial strategy for the treatment of Gram-positive infections for some 25 years. However, in recent years there has been a review of the traditional thrice-daily administration regimen in favor of an extended dosing interval strategy that takes into account the individual patient's renal function. The general recommendations that have been provided to date have been adopted in various ways internationally. These approaches were a matter of discussion for the Clinical Pharmacokinetics Committee of the International Association of Therapeutic Drug Monitoring and Clinical Toxicology at its congress (Vancouver, Canada; November 1997), and will again be a workshop issue at the Cairns (Australia) congress of the Association (September 1999). The present report provides examples of how these practices have been applied at a group of centers from Canada (2 centers), The Netherlands, Egypt, and Australia. These reports demonstrate a variety of approaches and highlight the need for further research for assessing clinical outcomes from different dosing strategies.

ISSN:0163-4356    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

Perhexiline is a prophylactic antianginal agent particularly useful in patients whose angina is poorly controlled or refractory to conventional drug regimens. Although perhexiline can cause serious hepatic and neurological toxicity, maintaining trough plasma concentrations between 0.15-0.60 mg/L minimizes the risk of toxicity while providing relief of angina symptoms in a majority of patients. All pathology laboratories are required to participate in interlaboratory proficiency testing (PT) programs. The authors therefore initiated a monthly PT program to assess the performance of Australian laboratories measuring perhexiline (n = 8). PT specimens included perhexiline-spiked drug-free human plasma and pooled plasma from patients administered perhexiline. The performance of 8 Australian laboratories participating in the program was examined over a 30-month period. The mean relative standard deviation of the group was 18.2%. All centers performed well with respect to accuracy, achieving mean percentage bias within ±8% of target perhexiline concentrations. The usefulness of the PT program was highlighted by the identification of two laboratories with an unacceptable degree of variability (up to 30% of results varied more than ±55% from the target concentration), and the identification of potential analytical problems with the use of perhexiline metabolite concentrations for determining patients' hydroxylator status. Continued and improved use of PT by pathology laboratories is essential to ensuring the safe and effective clinical use of perhexiline.

ISSN:0163-4356    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

The pharmacokinetics of vancomycin was investigated in adult ICU patients after the first administration and at steady state. Then the predictive performance of a two-compartment Bayesian forecasting program was assessed in these patients by using population-based parameters and three non steady state vancomycin concentrations as feedback information. Finally a prospective investigation was carried out to search potential covariates. At steady state, a significant decrease (around 30%) in clearance (CL) was observed, while creatinine clearance (CLcr) was stable and a significant increase (around 30%) in volume of distribution (Vss) was observed. A two-fold increase in elimination half-life was found. CL was weakly correlated with CLcr at onset of therapy and at steady state. The Bayesian program tended to over-predict vancomycin peak and trough concentrations. A larger mean prediction error and a poorer precision were observed when population-based parameter estimates were used (no feedback) compared to feedback prediction, but the differences were not significant. Mechanical ventilation and concurrent opioid therapy may be pertinent covariates of vancomycin pharmacokinetics. The current work has shown that vancomycin pharmacokinetics in ICU patients displayed a significant variability and a significant change in both clearance and distribution during the course of therapy. Further investigation is necessary to clarify these findings. Moreover, the use of the Bayesian forecasting PKS program in our patients led to a prediction with low bias but rather poor precision. This outcome highlights the need to implement a population modeling approach, to determine the vancomycin pharmacokinetic parameters and covariates in our ICU patients, and to apply this information to provide more accurate concentration predictions.

ISSN:0163-4356    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

Indinavir is a specific and potent HIV protease inhibitor. A new column liquid chromatographic method for the determination of this drug is described. This assay was developed for the clinical monitoring of trough concentrations in AIDS patients, using a 1-mL plasma sample volume. Determination of indinavir was made by a rapid solid-phase extraction procedure with the new polymeric Oasis HLB sorbent followed by a reversed-phase liquid chromatography and a UV detection at 210 nm. A weighted least squares linear regression (weighting factor = 1/ywherey= peak height ratio) was used to calculate the equation relating the peak-height ratio of the drug and the internal standard to the concentration of indinavir in the range 10-800 ng/mL (0.014-1.124 μM). At the lower limit of quantification (10 ng/mL), the mean accuracy was 102 ± 7% and 104 ± 11% for within- and between-day analysis, respectively. The limit of detection, based on a signal-to-noise ratio of 2:1, was 4 ng/mL (0.006 μM). Compounds of interest were eluted from the extraction cartridges with 300 μL of mobile phase, and mean absolute recoveries of indinavir and internal standard were 66.4% and 80.3%, respectively. No metabolite of indinavir was found to co-elute with the drug or its internal standard. Among the tested drugs, especially nucleoside analogues and the other protease inhibitors used in clinical care, none was found to interfere with the assay at this time. This simple and selective method is suitable for therapeutic indinavir monitoring.

ISSN:0163-4356    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

A simple, specific, sensitive, and rapid method has been developed and validated for the determination of sparfloxacin in human plasma and urine. The assay consisted of reversed-phase HPLC with ultraviolet detection. Plasma proteins were efficiently removed by precipitation with perchloric acid after the addition of grepafloxacin as an internal standard. For the urine samples, the only required sample preparation was dilution. Separation was achieved on a C18reversed-phase column. The quantification limit was 0.025 mg/L in plasma and 0.5 mg/L in urine. The coefficients of variation (CV) were less than 10% for intra-day and inter-day analyses. The recovery of sparfloxacin added to plasma and urine ranged from 96.7% to 97.9%. The method has been successfully applied to pharmacokinetic studies.

ISSN:0163-4356    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

In recent years, it has become clear that the presence of high concentrations of 1-OH midazolam glucuronide is probably the cause of unexplained prolonged midazolam comas in patients with poor renal function. Until recently, only indirect methods for the analysis of this glucuronide were known, which had several disadvantages, such as a long analysis period (>6 hours). This article describes the validation of a method for the direct analysis of this compound in human serum, using reversed-phase ion-pair high-performance liquid chromatography (HPLC) in combination with solid phase extraction. The intraday and interday coefficients of variation have values below 6% for different possible serum concentrations. The limit of quantification (0.1 mg/L) is much lower than concentrations found in patients with a coma caused by the accumulation of 1-OH midazolam glucuronide. Recovery of 1-OH midazolam glucuronide is almost 100% at three different serum concentrations. Linearity is confirmed for normal serum levels (<1 mg/L) and for serum levels that might occur in patients with impaired renal function (<20 mg/L). Detection is performed at 254 nm with a diode array detector, which can also be used to check the peak purity in case of unexpected impurities.

ISSN:0163-4356    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

Minimizing the risk for infection to laboratory staff from a contaminated blood sample is a major safety goal in the clinical laboratory. One dangerous pathogen, the human immunodeficiency virus (HIV), can be deactivated by heating sera at 56°C for 30 minutes. The authors previously reported that if serum was subjected to those conditions, the concentrations of the nine most commonly monitored drugs were not altered, whereas phenytoin and carbamazepine concentrations were reduced slightly. Monitoring free phenytoin, free valproic acid, and free carbamazepine concentrations is strongly recommended for patients with uremia, liver disease, and hypoalbuminemia. Because drug protein binding can be affected by temperature, the authors investigated the effect on free drug concentrations of sera heated to levels necessary for deactivation of the HIV virus. They measured total and free drug concentrations in serum pools prepared from patients receiving phenytoin, valproic acid, and carbamazepine. Serum pools were heated at 56°C for 30 minutes and then brought to room temperature. The total and free drug concentrations were measured immediately after heating and then at 20- and 45-minute intervals. The concentrations of free phenytoin and free valproic acid were significantly higher after heat treatment. However, after equilibration of sera at room temperature for 20 minutes, the free concentrations of phenytoin were comparable to preheating values, although total phenytoin concentrations (Serum Separator Tubes) were reduced slightly. In contrast, free valproic acid concentrations did not return to the original levels even after 45 minutes. Free carbamazepine concentrations did not change even immediately after heating. However, total carbamazepine concentrations were reduced slightly when sera were heated in serum separator tubes (SST Tubes).

ISSN:0163-4356    

出版商:OVID    

年代:1999

数据来源: OVID

ISSN:0163-4356    

出版商:OVID    

年代:1999

数据来源: OVID

ISSN:0163-4356    

出版商:OVID    

年代:1999

数据来源: OVID

ISSN:0163-4356    

出版商:OVID    

年代:1999

数据来源: OVID