Population pharmacokinetics of a posaconazole tablet formulation in transplant adult allogeneic stem cell recipients

Peña-Lorenzo, Diego; Rebollo, Noemí; Sánchez-Hernández, José Germán; Castañeda, Aránzazu Zarzuelo; Vázquez-López, Lourdes; Otero, María José; Pérez-Blanco, Jonás Samuel

doi:10.1016/j.ejps.2021.106049

Cited by 11 publications

(25 citation statements)

References 35 publications

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“…A total of 204 papers were initially retrieved from the databases. After screening according to the predetermined inclusion and exclusion criteria, 13 PopPK models (M1-M13) published between 2010 and 2022 were retained in this review 18,[23][24][25][26][27][28][29][30][31][32][33][34] . The screening process of the study is shown in Figure 1.…”

Section: Overview Of Studiesmentioning

confidence: 99%

“…With the exception of three studies that also included healthy volunteers 18,28,30 , the other studies included only patients with different pathological states such as obesity, immune deficiency, hematological malignancies, and pulmonary fibrosis. Nine 18,23,[25][26][27][28]30,31,34 studies included adults, three 29,32,33 included children, and one included 24 both. Of the 11 studies with oral formulations of posaconazole, three 18,[23][24][25][26]33 were with oral suspensions, four 27,28,31,32 with delayed-release tablets, and one 29 was on both oral suspension and delayed-release tablets.…”

Section: Overview Of Studiesmentioning

confidence: 99%

“…Nine 18,23,[25][26][27][28]30,31,34 studies included adults, three 29,32,33 included children, and one included 24 both. Of the 11 studies with oral formulations of posaconazole, three 18,[23][24][25][26]33 were with oral suspensions, four 27,28,31,32 with delayed-release tablets, and one 29 was on both oral suspension and delayed-release tablets. The two 30,34 remaining studies were conducted on intravenous formulations in the obese population and in critically ill patients treated with extracorporeal membrane oxygenation.…”

Section: Overview Of Studiesmentioning

confidence: 99%

“…With reference to absorption, six 18,23,25,27,29,33 models were described in terms of first-order absorption and two 18,33 with a lag time characterizing the absorption delay 18,33 . Out of the five [27][28][29]31,32 studies using delayed-release tablets, two 28,31 studies were described with sequential zero first-order absorption. The mode of absorption for the remaining five 24,26,30,32,34 studies was not mentioned.…”

Section: Structural Modelmentioning

confidence: 99%

“…Therefore, considering the inter-and intra-individual differences of posaconazole, the interactions between drugs, and the effect of serum drug concentration on efficacy, routine therapeutic drug monitoring (TDM) of posaconazole is recommended to ensure the adequate exposure required to achieve maximum efficacy for prophylaxis or treatment 19 . Some population pharmacokinetics (PopPK) models 18,[23][24][25][26][27][28][29][30][31][32][33][34] of posaconazole have been developed to better describe the PK characteristics of posaconazole in different target populations and to assist in adjusting the dosing regimen 35 . A review published in 2020 22 has summarized the PK parameters of eight of these models.…”

Section: Introductionmentioning

confidence: 99%

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A review of population pharmacokinetic models of posaconazole

Ding

Huang

Sun

et al. 2022

Preprint

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Aims: Posaconazole is often used for the prophylaxis and treatment of invasive fungal infections (IFI). However, intra- and inter-individual differences and drug interactions affect the efficacy and safety of posaconazole. Precision dosing of posaconazole based on the population pharmacokinetic (PopPK) model may assist in making significant clinical decisions. This review aimed to comprehensively summarize the published PopPK models of posaconazole and analyze covariates that significantly influence posaconazole exposure. Methods: Articles published until May 2022 for PopPK analysis of posaconazole were searched in PubMed and EMBASE databases. Demographic characteristics, model characteristics, and results of PopPK analysis were extracted from the selected articles. In addition, the steady-state pharmacokinetic profiles of posaconazole were simulated at different covariate levels and dosing regimens. Results： Out of the 13 studies included in our review, nine studies included adults, three included children, and one included both adults and children. All oral administration models were one-compartment models, and all intravenous administration models were two-compartment models. Body weight, proton pump inhibitors, and incidence of diarrhea were found to be important covariates. In addition, age, sex, total protein, rifampin, phenytoin, intake of nutritional supplements, levels of bilirubin and gamma-glutamyl transferase, and administration of chemotherapy also appeared as covariates in several PopPK models. Conclusion: Posaconazole exposure was found to be influenced by various factors such as the type of formulation, the incidence of diarrhea, body weight, and use of concomitant medications. It was concluded that routine therapeutic drug monitoring was required for dose adjustment and in promoting individualized dosing.

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Section: Overview Of Studiesmentioning

confidence: 99%

Section: Overview Of Studiesmentioning

confidence: 99%

Section: Overview Of Studiesmentioning

confidence: 99%

Section: Structural Modelmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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A review of population pharmacokinetic models of posaconazole

Ding

Huang

Sun

et al. 2022

Preprint

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Whole Body Physiologically Based Pharmacokinetic Model to Explain A Patient With Drug–Drug Interaction Between Voriconazole and Flucloxacillin

Abdullah-Koolmees,

van den Nieuwendijk,

Hoope

et al. 2024

Eur J Drug Metab Pharmacokinet

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Personalized Antifungal Therapy Through Model-Informed Precision Dosing of Posaconazole

Jansen,

Snijdelaar,

Keizer

et al. 2024

Clin Pharmacokinet

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Background and Objective Posaconazole is a pharmacotherapeutic pillar for prophylaxis and treatment of invasive fungal diseases. Dose individualization is of utmost importance as achieving adequate antifungal exposure is associated with improved outcome. This study aimed to select and evaluate a model-informed precision dosing strategy for posaconazole. Methods Available population pharmacokinetic models for posaconazole administered as a solid oral tablet were extracted from the literature and evaluated using data from a previously published prospective study combined with data collected during routine clinical practice. External evaluation and selection of the most accurate and precise model was based on graphical goodness-of-fit and predictive performance. Measures for bias and imprecision included mean percentage error (MPE) and normalized relative root mean squared error (NRMSE), respectively. Subsequently, the best-performing model was evaluated for its a posteriori fit-for-purpose and its suitability in a limited sampling strategy. Results Seven posaconazole models were evaluated using 764 posaconazole plasma concentrations from 143 patients. Multiple models showed adequate predictive performance illustrated by acceptable goodness-of-fit and MPE and NRMSE below ± 10% and ± 25%, respectively. In the fit-for-purpose analysis, the selected model showed adequate a posteriori predictive performance. Bias and imprecision were lowest in the presence of two prior measurements. Additionally, this model showed to be useful in a limited sampling strategy as it adequately predicted total posaconazole exposure from one (non-)trough concentration. Conclusion We validated an MIPD strategy for posaconazole for its fit-for-purpose. Thereby, this study is an important first step towards MIPD-supported posaconazole dosage optimization with the goal to improve antifungal treatment in clinical practice. Supplementary Information The online version contains supplementary material available at 10.1007/s40262-024-01361-8.

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Population pharmacokinetics of a posaconazole tablet formulation in transplant adult allogeneic stem cell recipients

Cited by 11 publications

References 35 publications

A review of population pharmacokinetic models of posaconazole

A review of population pharmacokinetic models of posaconazole

Whole Body Physiologically Based Pharmacokinetic Model to Explain A Patient With Drug–Drug Interaction Between Voriconazole and Flucloxacillin

Personalized Antifungal Therapy Through Model-Informed Precision Dosing of Posaconazole

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