Population Pharmacokinetics in China: The Dynamics of Intravenous Voriconazole in Critically Ill Patients with Pulmonary Disease

Chen, Wenying; Xie, Hui; Liang, Fenghua; Meng, Dong; Rui, Jianzhong; Yin, Xu; Zhang, Tiantian; Xiao, Xilong; Cai, Shaohui; Liu, Xiaoqing; Li, Yimin

doi:10.1248/bpb.b14-00768

Cited by 21 publications

(30 citation statements)

References 26 publications

(25 reference statements)

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“…The population estimate of CL (2.88 l·h −1 ) in the present study is similar to the reported value for lung transplant recipients (3.45 l·h −1 ) but lower than that of other patients with IFIs . The lower CL possibly results from the unrecovered renal function of the RTRs, with a lower baseline creatinine CL (mean ± standard deviation) of (47.3 ± 23.4) ml·min −1 .…”

Section: Discussionsupporting

confidence: 82%

See 1 more Smart Citation

Population pharmacokinetics of voriconazole and CYP2C19 polymorphisms for optimizing dosing regimens in renal transplant recipients

Lin

Yan

et al. 2018

Brit J Clinical Pharma

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Section: Discussionsupporting

confidence: 82%

“…A growing number of studies have shown that VRC exhibits significant exposure–response relationships for efficacy and toxicity; the target trough concentrations (C min ) have been identified . Hence, therapeutic drug monitoring (TDM) is now widely recommended to optimize clinical outcomes .…”

Section: Introductionmentioning

confidence: 99%

Population pharmacokinetics of voriconazole and CYP2C19 polymorphisms for optimizing dosing regimens in renal transplant recipients

Lin

Yan

et al. 2018

Brit J Clinical Pharma

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“…The initial database search yielded 152 publications, and after selection, a total of 16 studies involving 1411 participants met the inclusion criteria [11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26]. The population characteristics of the included studies are summarized in Table 1.…”

Section: Resultsmentioning

confidence: 99%

“…CYP 2C19 genotyping data were included in 11 articles [12, 14-18, 21, 23-26]. Among the 16 publications describing a population pharmacokinetic model for voriconazole, 11 described studies conducted in adult participants, [11][12][13][14][15][16][17][18][19][20][21] whereas four of the studies were conducted in pediatric populations, [22][23][24][25] and the remaining study by Friberg et al [26] included both adult and pediatric patients. The studied populations consisted of healthy volunteers and patients who were administered voriconazole for the treatment or prophylaxis of fungal infections, possibly accompanied by additional pathologies, including pulmonary diseases, organ transplant, and hematological malignancies.…”

Section: Resultsmentioning

confidence: 99%

Voriconazole: A Review of Population Pharmacokinetic Analyses

Shi

Xiao²,

Mao

et al. 2019

Clin Pharmacokinet

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Numerous population pharmacokinetic studies on voriconazole have been conducted in recent years. This review aimed to comprehensively summarize the population pharmacokinetic models for voriconazole and to determine which covariates have been identified and which remain to be explored. We searched the PubMed and EMBASE databases from inception to March 2018 for population pharmacokinetic analyses of voriconazole using the nonlinear mixed-effect method. A total of 16 studies were included in this review, of which 11 models were described in adult populations, four were described in pediatric populations, and the remaining study included both adult and pediatric populations. The absorption profiles of voriconazole in both adult and pediatric studies were best described as first-order absorption models. The typical distribution volumes were similar in adult and pediatric patients, but the estimated clearances in pediatric patients were significantly higher than those in adult patients. The most commonly identified covariates were body weight, the cytochrome P450 2C19 genotype, liver function, and concomitant medications. Only one study evaluated the model using an external method. Further population pharmacokinetic studies on pediatric patients aged younger than 2 years are warranted. Furthermore, new or controversial potential covariates, such as inflammation, the cytochrome P450 3A4 genotype, concomitant medications (particularly various types and dosages of proton pump inhibitors and glucocorticoids), and various measures of body weight, should be tested because the unexplained variability remains relatively high. In addition, previously published models should be externally evaluated, and the predictive performance of the various models should be compared.

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“…The inflammatory process, quantified by the CRP level, seems to be associated with a reduction in the metabolizing enzymes of cytochrome P450 and, therefore, with a decrease in the clearance of this drug. High bilirubin values have also been correlated with the plasma concentrations of voriconazole, with those patients showing increases in bilirubin values also having a higher risk of toxicity. In the present study, hypoalbuminemia has not been identified as a potential variable of voriconazole exposure.…”

Section: Discussionmentioning

confidence: 99%

Impact of voriconazole plasma concentrations on treatment response in critically ill patients

et al. 2019

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Summary What is known and objective Several authors have demonstrated the relationship between voriconazole concentrations and the risk of therapeutic failure and adverse events However, the information about voriconazole concentrations in the critically ill patient is scarce. The aim of this study was to analyse the plasma concentrations and pharmacokinetic behaviour of voriconazole in critically ill patients and their association with the treatment response and development of toxicity. Methods A prospective, observational study was conducted. Patients admitted to an intensive care unit and on treatment with intravenous voriconazole were included. Plasma concentrations were measured between days 4 and 7 from the start of the treatment. The pharmacokinetic analysis was performed using the NONMEM® software. A regression model was used to evaluate the variables associated with the values outside the therapeutic range, as well as the relationship between the plasma concentrations and the treatment response and the development of hepatotoxicity. Results and discussion A total of 33 patients were included. Plasma concentrations outside the therapeutic range (1‐5.5 mg/L) were observed in 15 patients, being above the established range in 9 (27.3%) cases, and below it in 6 (18.2%) cases. The presence of a bilirubin value of >1.5 mg/dL and a C‐reactive protein >100 mg/dL was associated with supra‐therapeutic concentrations. Voriconazole concentrations greater than 5.5 mg/dL were associated with the development of hepatotoxicity. What is new and conclusions There is a wide variation in voriconazole concentrations in critically ill patients, being associated with a high frequency of adverse events. Close monitoring of these values is required in order to decrease the risk of therapeutic failure and toxicity.

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Population Pharmacokinetics in China: The Dynamics of Intravenous Voriconazole in Critically Ill Patients with Pulmonary Disease

Cited by 21 publications

References 26 publications

Population pharmacokinetics of voriconazole and CYP2C19 polymorphisms for optimizing dosing regimens in renal transplant recipients

Population pharmacokinetics of voriconazole and CYP2C19 polymorphisms for optimizing dosing regimens in renal transplant recipients

Voriconazole: A Review of Population Pharmacokinetic Analyses

Impact of voriconazole plasma concentrations on treatment response in critically ill patients

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