Therapeutic drug monitoring and use of an adjusted body weight strategy for high-dose voriconazole therapy

Richards, Patrick; Dang, Kimberlyn M.; Kauffman, Carol A.; Stalker, Kay Lyn; Sudekum, David; Kerr, Lisa; Brinker-Bodley, Michelle; Cheriyan, Beena; West, Nina; Collins, Curtis D.; Polega, Shikha; Malani, Anurag N.

doi:10.1093/jac/dkw550

Cited by 13 publications

(11 citation statements)

References 14 publications

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“…However, an actual body weight-adjusted dosing regimen may not be feasible for obese patients, as this would lead to high VRC concentrations (Davies-Vorbrodt et al, 2013;Koselke et al, 2012). A dosing regimen based on adjusted body weight has been proposed (Davies-Vorbrodt et al, 2013;Koselke et al, 2012;Richards et al, 2017), and further studies are needed. In the current study, no obese patient (body mass index !30 kg/m 2 ) was observed.…”

Section: Discussionmentioning

confidence: 99%

Pharmacokinetics of intravenous voriconazole in patients with liver dysfunction: A prospective study in the intensive care unit

Lin

Huang

et al. 2020

International Journal of Infectious Diseases

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To characterize the pharmacokinetics (PK) of intravenous voriconazole (VRC) in critically ill patients with liver dysfunction. Methods: Patients with liver dysfunction in the intensive care unit (ICU) were included prospectively. The Child-Pugh score was used to categorize the degree of liver dysfunction. The initial intravenous VRC dosing regimen comprised a loading dose of 300 mg every 12 h for the first 24 h, followed by 200 mg every 12 h. The first PK curves (PK curve 1) were drawn within one dosing interval of the first dose for 17 patients; the second PK curves (PK curve 2) were drawn within one dosing interval after a minimum of seven doses for 12 patients. PK parameters were estimated by non-compartmental analysis. Results: There were good correlations between the area under the curve (AUC 0-12 ) of PK curve 2 and the corresponding trough concentration (C 0 ) and peak concentration (C max ) (r 2 = 0.951 and 0.963, respectively; both p < 0.001). The median half-life (t 1/2 ) and clearance (CL) of patients in Child-Pugh class A (n = 3), B (n = 5), and C (n = 4) of PK curve 2 were 24.4 h and 3.31 l/h, 29.1 h and 2.54 l/h, and 60.7 h and 2.04 l/h, respectively. In the different Child-Pugh classes, the CL (median) of PK curve 2 were all lower than those of PK curve 1. The apparent steady-state volume of distribution (V ss ) of PK curve 1 was positively correlated with actual body weight (r 2 = 0.450, p = 0.004). The median first C 0 of 17 patients determined on day 5 was 5.27 (2.61) mg/ml, and 29.4% of C 0 exceeded the upper limit of the therapeutic window (2-6 mg/ml). Conclusions:The CL of VRC decreased with increasing severity of liver dysfunction according to the Child-Pugh classification, along with an increased t 1/2 , which resulted in high plasma exposure of VRC. Adjusted dosing regimens of intravenous VRC should be established based on Child-Pugh classes for these ICU patients, and plasma concentrations should be monitored closely to avoid serious adverse events.

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Section: Discussionmentioning

confidence: 99%

Pharmacokinetics of intravenous voriconazole in patients with liver dysfunction: A prospective study in the intensive care unit

Lin

Huang

et al. 2020

International Journal of Infectious Diseases

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“…Therefore, dosing based simply on the actual WT may not be feasible, especially for obese patients. An adjusted WT dosing strategy has been proposed but needs further study.…”

Section: Discussionmentioning

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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“…Initial supratherapeutic levels have been obtained in obese patients (BMI .35 kg/m 2 ) with 12 mg/kg, whereas maintenance doses (8.5 mg/kg) were similar to those in nonobese patients. 139 Intravenous VRZ doses should be based on ABW or IBW (rather than TBW) and careful TDM should be implemented. 138 Dose adjustment to lean body weight (LBW) has been proposed for FCZ, but not VRZ a priori, but caution is required in the use of ABW (possible risk of higher levels of exposure in poor CYP2C19 metabolizers).…”

Section: Coexisting Factors Obesity Bariatric Surgerymentioning

confidence: 99%

Antifungal Drugs TDM: Trends and Update

Kably

Launay

Derobertmasure

et al. 2022

Therapeutic Drug Monitoring

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The increasing burden of invasive fungal infections results in growing challenges to antifungal (AF) therapeutic drug monitoring (TDM). This review aims to provide an overview of recent advances in AF TDM. Methods:We conducted a PubMed search for articles during 2016-2020 using "TDM" or "pharmacokinetics" or "drug-druginteraction" with "antifungal," consolidated for each AF. Selection was limited to English language articles with human data on drug exposure.Results: More than 1000 articles matched the search terms. We selected 566 publications. The latest findings tend to confirm previous observations in real-life clinical settings. The pharmacokinetic variability related to special populations is not specific but must be considered. AF benefit-to-risk ratio, drug-drug interaction (DDI) profiles, and minimal inhibitory concentrations for pathogens must be known to manage at-risk situations and patients. Itraconazole has replaced ketoconazole in healthy volunteers DDI studies. Physiologically based pharmacokinetic modeling is widely used to assess metabolic azole DDI. AF prophylactic use was studied more for Aspergillus spp. and Mucorales in oncohematology and solid organ transplantation than for Candida (already studied). Emergence of central nervous system infection and severe infections in immunocompetent individuals both merit special attention. TDM is more challenging for azoles than amphotericin B and echinocandins. Fewer TDM requirements exist for fluconazole and isavuconazole (ISZ); however, ISZ is frequently used in clinical situations in which TDM is recommended. Voriconazole remains the most challenging of the AF, with toxicity limiting high-dose treatments. Moreover, alternative treatments (posaconazole tablets, ISZ) are now available.Conclusions: TDM seems to be crucial for curative and/or longterm maintenance treatment in highly variable patients. TDM poses fewer cost issues than the drugs themselves or subsequent treatment issues. The integration of clinical pharmacology into multidisciplinary management is now increasingly seen as a part of patient care.

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Therapeutic drug monitoring and use of an adjusted body weight strategy for high-dose voriconazole therapy

Cited by 13 publications

References 14 publications

Pharmacokinetics of intravenous voriconazole in patients with liver dysfunction: A prospective study in the intensive care unit

Pharmacokinetics of intravenous voriconazole in patients with liver dysfunction: A prospective study in the intensive care unit

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

Antifungal Drugs TDM: Trends and Update

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