Pharmacokinetic Optimisation of Vancomycin Therapy

Leader, W. G.; Chandler, M. H. H.; Castiglia, Mary

doi:10.2165/00003088-199528040-00005

Cited by 89 publications

(30 citation statements)

References 72 publications

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“…1) Vancomycin, a glycopeptide antibiotic, has been used to treat MRSA infections, and it requires effective therapeutic drug monitoring (TDM) during treatment period especially to reduce the incidences of nephrotoxicity by controlling its serum concentration within the therapeutic range. [2][3][4] The pharmacokinetics of vancomycin in MRSA-infected patients has been studied, [5][6][7][8][9][10] and population pharmacokinetic parameters were reported in adult Japanese patients. 11) More recently, an empirical Bayesian method has been widely applied to TDM data, 12) and the predictability of the Bayesian forecasting methodology for vancomycin with the population pharmacokinetic parameters in Japanese patients was examined.…”

mentioning

confidence: 99%

A Retrospective Analysis of Vancomycin Pharmacokinetics in Japanese Cancer and Non-cancer Patients Based on Routine Trough Monitoring Data

Omote

Yano

Hashida

et al. 2009

Biological & Pharmaceutical Bulletin

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The pharmacokinetics of vancomycin was retrospectively examined based on trough concentrations obtained during routine therapeutic drug monitoring to examine possible pharmacokinetic differences between adult Japanese cancer and non-cancer patients with various degrees of renal function. A total of 231 data points from 65 cancer patients and 41 non-cancer patients were collected, and patients' background, vancomycin dose, and vancomycin clearance estimated by an empirical Bayesian method were summarized. Regarding the patients' characteristics and clinical laboratory test data, no clear differences were found between the two groups. The relationship between vancomycin clearance and creatinine clearance were similar between the groups, suggesting little effect of malignancy on vancomycin clearance. After the sub-group comparisons regarding fluid retention and cancer type, no clear differences were found in the vancomycin clearance versus creatinine clearance relationship. We conclude that the initial dose of vancomycin should not necessarily be adjusted for cancer patients. For individualized vancomycin-based therapy, dose adjustment at the appropriate time is important according to information from routine therapeutic drug monitoring and clinical laboratory tests, and to observations of the efficacy, nephrotoxicity, and other conditions in each patient.

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mentioning

confidence: 99%

A Retrospective Analysis of Vancomycin Pharmacokinetics in Japanese Cancer and Non-cancer Patients Based on Routine Trough Monitoring Data

Omote

Yano

Hashida

et al. 2009

Biological & Pharmaceutical Bulletin

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“…The correlations between doses and pharmacokinetic profiles of glycopeptides in humans are well described, but the correlation between the pharmacokinetic profile and the effect of treatment of patients has not been fully elucidated (1,12,16,26,28). Because of fear of toxic effects, it was previously recommended that serum drug concentrations be monitored regularly during glycopeptide therapy, at least as trough concentrations but eventually also as peak concentrations (1,6,7,12,16,26,28,29).…”

mentioning

confidence: 99%

“…Because of fear of toxic effects, it was previously recommended that serum drug concentrations be monitored regularly during glycopeptide therapy, at least as trough concentrations but eventually also as peak concentrations (1,6,7,12,16,26,28,29). The effect of treatment has been correlated to dose and serum drug concentrations, but most studies have been retrospective and have focused on treatment failures and the correlation to serum drug concentrations (1,6,7,12,16,26,28,29). It has not been possible to conclude which one or more of the pharmacokinetic or pharmacodynamic (PK/PD) parameters are the most important and best predictors for the effects of treatment in humans (1,6,12,16,26,28).…”

mentioning

confidence: 99%

Pharmacodynamics of Glycopeptides in the Mouse Peritonitis Model ofStreptococcus pneumoniaeorStaphylococcus aureusInfection

Knudsen

Fuursted

Raber

et al. 2000

Antimicrob Agents Chemother

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The emergence of resistance to various antibiotics in pneumococci leaves the glycopeptides as the only antibiotics against which pneumococci have no resistance mechanism. This situation has led to a renewed interest in the use of glycopeptides. It has not yet been possible to conclude which one or more of the pharmacokinetic or pharmacodynamic (PK/PD) parameters are the most important and best predictors for the effects of treatment with glycopeptides in animal models or in humans. We used the mouse peritonitis model with immunocompetent mice and with Staphylococcus aureus and Streptococcus pneumoniae as infective organisms. A wide spectrum of different treatment regimens with vancomycin and teicoplanin was tested to study the pharmacodynamics of these drugs. In studies in which the single dose that protected 50% of lethally infected mice (ED 50 ) was given as one dose or was divided into two doses, survival was significantly decreased when the dose was divided. The only statistically significant correlations between the percentage of survival of the mice after 6 days and each of the PK/PD parameters were for peak concentration (C max )/MIC and S. aureus and for the free fraction of C max (C max-free )/MIC and S. pneumoniae. For S. pneumoniae, the ED 50 for different dosing regimens increased with the number of doses given; e.g., the single-dose ED 50 s for vancomycin and teicoplanin were 0.65 and 0.45 mg/kg, respectively, but the ED 50 s for dosing regimens with 2-h doses given for 48 h were 6.79 and 5.67 mg/kg, respectively. In experiments with 39 different vancomycin dosing regimens and 40 different teicoplanin dosing regimens against S. pneumoniae, the different PK/PD parameters were analyzed using logistic regression. The C max-free /MIC was one of two parameters that best explained the effect for both drugs; for vancomycin, the other important parameter was the AUC/MIC, and for teicoplanin, the other parameter was the time the free fraction of the drug is above the MIC. The effect analyzed as a function of C max-free /MIC disclosed thresholds with shifts from almost no effect to full effect at ratios of five to six for vancomycin and two to three for teicoplanin.

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“…1 4) VCM is mainly eliminated from the body via the kidney. 5) Therefore altered renal function is very important in modifying VCM pharmacokinetics. 6) Therapeutic drug monitoring (TDM) is necessary to increase the e‹cacy of VCM in the treatment of MRSA infection.…”

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confidence: 99%

Correlation of Pharmacokinetic Parameters with Serum Vancomycin Concentration in Elderly Patients with Malignancies

2010

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Vancomycin (VCM) is a glycopeptide antibiotic that is generally used to treat methicillin-resistant Staphylococcus aureus (MRSA). Recently, it has been reported that VCM clearance (CL) is signiˆcantly higher in elderly patients and infants and children with malignancies, compared with those without malignancies. We have treated many patients with a variety of malignant tumors in whom serum VCM concentrations were found to be moderately lower during therapeutic drug monitoring (TDM). The aim of this study was to determine whether the presence of malignant tumors in‰uences trough concentrations of VCM and VCM pharmacokinetics in elderly patients during treatment for MRSA infection. Comparison of the clinical characteristics and VCM pharmacokinetic parameters between patients with and without malignancies was undertaken in 49 elderly Japanese patients infected with MRSA. The mean trough concentration of VCM in patients with malignancies was signiˆcantly lower than that in patients without malignancies. Our results showed signiˆcantly higher values of VCM CL and volume of distribution and a shorter elimination half-life in patients with malignancies. Univariate logistic regression analysis of the pharmacokinetic parameters indicated that VCM CL contributed as a signiˆcant factor independent of the relation to malignant tumor. In conclusion, it is suggested that the therapeutic eŠects and side eŠects of VCM should be actively monitored using TDM, because concentrations may decrease when CL increases in VCM therapy for elderly patients with malignant tumors.

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Pharmacokinetic Optimisation of Vancomycin Therapy

Cited by 89 publications

References 72 publications

A Retrospective Analysis of Vancomycin Pharmacokinetics in Japanese Cancer and Non-cancer Patients Based on Routine Trough Monitoring Data

A Retrospective Analysis of Vancomycin Pharmacokinetics in Japanese Cancer and Non-cancer Patients Based on Routine Trough Monitoring Data

Pharmacodynamics of Glycopeptides in the Mouse Peritonitis Model ofStreptococcus pneumoniaeorStaphylococcus aureusInfection

Correlation of Pharmacokinetic Parameters with Serum Vancomycin Concentration in Elderly Patients with Malignancies

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