Posaconazole Exposure-Response Relationship: Evaluating the Utility of Therapeutic Drug Monitoring

Dolton, Michael; Ray, John E.; Marriott, Deborah; McLachlan, Andrew J.

doi:10.1128/aac.05900-11

Cited by 136 publications

(131 citation statements)

References 59 publications

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“…Therapeutic drug monitoring of a patient's serum or plasma has been a useful tool to detect drug exposures outside of the therapeutic window and to help individualize a dosage regimen and treatment, increasing therapeutic efficacy, and decreasing side effects . Reported methods for the analysis of posaconazole are mostly high-performance liquid chromatography (HPLC) with mass spectrometry [13][14][15][16][17][18][19][20][21][22][23][24][25], ultraviolet [26][27][28][29][30][31] and fluorescence [32][33][34][35] detections. Mass spectrometry (MS) and tandem mass spectrometry (MS/MS) are superior in sensitivity and specificity to ultraviolet (UV) and fluorescence (FL) detections.…”

Section: Introductionmentioning

confidence: 99%

Determination of Posaconazole in Plasma/Serum by High-Performance Liquid Chromatography with Fluorescence Detection

Tang

2017

Separations

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Abstract:A sensitive high-performance liquid chromatographic (HPLC) method is described for the determination of posaconazole in human plasma/serum. The method is based on a single dilution step by treating the sample with methanol, and followed by the direct injection of the sample into the HPLC system. Posaconazole and internal standard ketoconazole in the methanol extract are subsequently analyzed by using a fluorescence (FL) detector at optimized wavelengths (excitation 245 nm and emission 380 nm). The method achieves a linear detector response for peak height measurements over the concentration range of 0.1-10 µg/mL which adequately covers the therapeutic range for appropriate patient monitoring. The chromatographic time is less than 8 min per injection, an improvement over most published HPLC/FL or HPLC/UV methods. The method's limit of quantitation, linearity, imprecision, and accuracy met all criteria required by the Guidance for Industry Bioanalytical Method Validation. In comparison to other published methods, the current method would be of interest to analytical and clinical laboratories because it employs simple, rapid, and cost-effective procedures.

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Section: Introductionmentioning

confidence: 99%

Determination of Posaconazole in Plasma/Serum by High-Performance Liquid Chromatography with Fluorescence Detection

Tang

2017

Separations

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“…Therapeutic drug monitoring is built on the strength of previously defined exposure–response relationships, which describe how changes in drug exposure affect selected measures of efficacy and/or tolerability 49, 50. When the best PK predictor of the response to therapy is unknown or insufficient validation of targets has been performed, therapeutic drug monitoring is of limited utility.…”

Section: Individualized Dosingmentioning

confidence: 99%

Use of Modeling and Simulation in the Design and Conduct of Pediatric Clinical Trials and the Optimization of Individualized Dosing Regimens

Barrett

Roberts

Sherwin

2015

CPT Pharmacometrics Syst. Pharmacol.

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Mathematical models of drug action and disease progression can inform pediatric pharmacotherapy. In this tutorial, we explore the key issues that differentiate pediatric from adult pharmacokinetic (PK) / pharmacodynamic (PD) studies, describe methods to calculate the number of participants to be enrolled and the optimal times at which blood samples should be collected, and therapeutic drug monitoring methods for individualizing pharmacotherapy. The development of pediatric‐specific drug dosing dashboards is also highlighted, with an emphasis on clinical‐relevance and ease of use.

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“…Challenges related to posaconazole treatment include availability only as a liquid formulation [8,9], multiple daily doses requiring administration with a high fat meal [10][11][12], erratic absorption [13], unclear exposure-response relationship, and questionable utility of therapeutic drug monitoring [14][15][16]. Voriconazole is a broad-spectrum triazole that has activity against both yeasts and molds with both oral and intravenous formulations available [17,18].…”

Section: Introductionmentioning

confidence: 99%

The incidence of invasive fungal infections in neutropenic patients with acute leukemia and myelodysplastic syndromes receiving primary antifungal prophylaxis with voriconazole

et al. 2013

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The objective of this study is to characterize the outcomes of primary antifungal prophylaxis with voriconazole in patients receiving intensive chemotherapy for acute myelogenous leukemia (AML) or myelodysplastic syndromes (MDS). We conducted a single center, retrospective, cohort study of consecutive adult patients with AML or MDS at Mayo Clinic between January 1, 2006 and July 1, 2010. The study included patients undergoing induction or first relapse combination chemotherapy who received voriconazole 200 mg orally twice daily as prophylaxis during the neutropenic phase. Patient records were evaluated until 30 days after neutrophil recovery for development of invasive fungal infection (IFI) as defined per EORTC/MSG 2008 criteria with computed tomography scans independently reviewed by a radiologist. Therapeutic drug monitoring and reasons for voriconazole discontinuation were documented. Twenty four episodes of IFI were detected among 165 consecutive patients for an overall incidence of 145 per 1000 patients. The incidence of IFI was 24, 42, and 78 per 1000 patients for proven, probable, and possible infection, respectively. Four patients developed proven IFI (n = 2 Aspergillus spp., n = 2 Rhizopus spp.). Serum voriconazole trough concentrations were available in 39 patients, and no statistically significant difference in voriconazole trough level was observed between those with versus without an IFI. Voriconazole prophylaxis was discontinued in 81 patients due to suspected IFI (n = 24), fever of unknown origin (n = 19), adverse events (n = 23), and other causes (n = 17). Voriconazole as primary IFI prophylaxis is safe and may be beneficial in AML/MDS patients receiving intensive chemotherapy. Am. J. Hematol. 88:283–288, 2013. © 2013 Wiley Periodicals, Inc.

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Posaconazole Exposure-Response Relationship: Evaluating the Utility of Therapeutic Drug Monitoring

Cited by 136 publications

References 59 publications

Determination of Posaconazole in Plasma/Serum by High-Performance Liquid Chromatography with Fluorescence Detection

Determination of Posaconazole in Plasma/Serum by High-Performance Liquid Chromatography with Fluorescence Detection

Use of Modeling and Simulation in the Design and Conduct of Pediatric Clinical Trials and the Optimization of Individualized Dosing Regimens

The incidence of invasive fungal infections in neutropenic patients with acute leukemia and myelodysplastic syndromes receiving primary antifungal prophylaxis with voriconazole

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