Observational Study of the Clinical Efficacy of Voriconazole and Its Relationship to Plasma Concentrations in Patients

Abstract

Volume 55, no. 10, p. 4782-4788, 2011. Page 4786: The x axis values for Fig. 2 were incorrect; the figure should appear as shown below. FIG. 2. Binomial data and linear logistic fit for investigator outcome versus the mean voriconazole free drug/MIC ratio for 404 patients. E, Data points separated as clinical success or clinical failure. Curves: ---, spline; --, line of predicted fit; ---, upper and lower 95% confidence intervals. The slope was significant at P ϭ 0.005. Note that the free ratio is 0.4 ϫ the ratio. Calculation: logit (P) ϭ (0.766 ϩ 0.139) ϫ log e free ratio, where P is the probability of response. 5415on May 9, 2018 by guest http://aac.asm.org/ Downloaded from

Combination of Voriconazole and Anidulafungin for Treatment of Triazole-Resistant Aspergillus fumigatus in an In Vitro Model of Invasive Pulmonary Aspergillosis

“…The risk of a submaximal antifungal effect resulting from subtherapeutic voriconazole concentrations may also be minimized. Voriconazole fails to achieve target plasma concentrations following standard regimens in a proportion of patients, who could potentially be protected by a second agent until dosage alterations are made (13,43).…”

Software for Dosage Individualization of Voriconazole for Immunocompromised Patients

“…to medically important molds have been engineered at a cost of less-predictable pharmacokinetics (17). Voriconazole is an ideal candidate for therapeutic drug monitoring for the following reasons: (i) there are well-established drug exposure-effect and drug exposure-toxicity relationships (7,8,10); (ii) there is evidence that therapeutic drug monitoring may lead to improved therapeutic outcomes (8,18); and (iii) voriconazole exhibits significant interpatient variability with classical nonlinear pharmacokinetics (12). While therapeutic drug monitoring may be a desirable adjunct to the routine use of voriconazole, at this time there are no algorithms that can be used to adjust the regimen to attain predefined serum concentration targets in an optimally precise manner.…”

“…Exposure-response and exposure-toxicity relationships are increasingly well described in experimental and clinical contexts (4)(5)(6). A trough concentration of Ն1 mg/liter is associated with improved clinical outcomes and survival in adults and children (7)(8)(9)(10). Furthermore, a trough concentration of Ͼ4.5 to 6 mg/liter is associated with an increased risk of both hepatotoxicity and central nervous system toxicity (8,9,11).…”

Optimizing antifungal choice and administration

“…Each of these drugs meet widely accepted criteria for TDM: unpredictable population PK, a relatively narrow therapeutic window, and a fairly well defined clinical therapeutic range 49,51 . TDM recommended trough concentrations for voriconazole and posaconazole efficacy are each approximately 41 mg/mL 50,51,[53][54][55][56][57] . A recommended trough 55 mg/mL has been recommended to limit the likelihood of voriconazole toxicity; a toxicity trough associated with posaconazole has not been defined 51 .…”