Predicting the Effects of Different Triazole Antifungal Agents on the Pharmacokinetics of Tamoxifen

Chen, Lu; Zhu, Liqin; Li, Mengxue; Li, Na; Fang, Qi; Wang, Nan

doi:10.1208/s12249-018-1219-5

Cited by 11 publications

(17 citation statements)

References 41 publications

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“…First-order absorption models were used for fluconazole, itraconazole, and ketoconazole. Physicochemical properties data of the 3 triazoles obtained from published articles 10,16 are shown in Table 1. For itraconazole, the apparent K m and V max values of CYP3A4 were 0.004 µM and 0.065 pmol/min/pmol, respectively.…”

Section: Methodsmentioning

confidence: 99%

“…The necessary physicochemical data used to develop the PBPK model were the following: molecular weight, acid dissociation constant, octanol/water partition coefficient, fraction unbound in plasma, solubility, blood-to-plasma concentration ratio, hydrogen bond donors, fraction unbound in gut, polar surface area, and effective permeability. These necessary parameters 10,16 are shown in Table 1. The crucial parameters were ascertained from Drug Bank (https://www.drugbank.ca/) published studies.…”

Section: Development and Validation Of The Cyclophosphamide Pbpk Modelmentioning

confidence: 99%

“…Triazole antifungal agents are widely used in clinical practice for IFIs. 10 Therefore, it is necessary to combine triazole antifungal agents with cyclophosphamide for cancer patients with IFIs. It is reported that cyclophosphamide, a prodrug, is metabolized into active metabolites by CYP2B6, CYP3A4, CYP2C9, and CYP2A6.…”

Section: Introductionmentioning

confidence: 99%

“…Summary of Physicochemical Properties of Fluconazole, Itraconazole, Ketoconazole, and Cyclophosphamide Input in Simulations 10,16,31. …”

mentioning

confidence: 99%

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The Influence of Different Triazole Antifungal Agents on the Pharmacokinetics of Cyclophosphamide

et al. 2020

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Background: Cyclophosphamide is one of the most important chemotherapeutic drugs. Known as a widely accepted treatment strategy, chemotherapy may damage the immune function of cancer patients; as a result, invasive fungal infections (IFIs) occur. Triazole antifungal agents are the most acceptable drugs for IFI treatment, especially those infections caused by chemotherapy. Objective: We aimed to investigate the effects of different triazole antifungal drugs, including fluconazole, itraconazole, and ketoconazole, on the pharmacokinetics (PK) of cyclophosphamide. In addition, we also characterize the potential drug-drug interactions (DDIs) between cyclophosphamide and various triazole antifungal drugs. Methods: The necessary pharmacokinetic parameters and physicochemical data were obtained from published studies. Physiologically based pharmacokinetic (PBPK) models were developed and validated in virtual subjects using Simcyp software. The validated PBPK models were used to evaluate potential DDIs between cyclophosphamide and different triazole antifungal agents in cancer patients. Triazole antifungal agents were simulated by oral administration, whereas cyclophosphamide was simulated by intravenous administration. Results: Simulated plasma concentration-time curves of fluconazole, itraconazole, ketoconazole, and cyclophosphamide were in good consistency with the observed profiles. Our results suggested that the pharmacokinetic parameters of cyclophosphamide were increased by various extents when coadministered with different triazole antifungals. The area under the plasma concentration-time curve of cyclophosphamide was increased when combined with fluconazole, itraconazole, or ketoconazole. Conclusions and Relevance: Ketoconazole had the greatest effect on the PK of cyclophosphamide among the 3 triazole antifungals. Our study provides clues that the toxicity and adverse drug reactions that are associated with cyclophosphamide should be closely monitored when coadministered with ketoconazole.

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Section: Methodsmentioning

confidence: 99%

Section: Development and Validation Of The Cyclophosphamide Pbpk Modelmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

“…Summary of Physicochemical Properties of Fluconazole, Itraconazole, Ketoconazole, and Cyclophosphamide Input in Simulations 10,16,31. …”

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confidence: 99%

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The Influence of Different Triazole Antifungal Agents on the Pharmacokinetics of Cyclophosphamide

et al. 2020

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“…According to the results of the physiologically based pharmacokinetic models, triazole agents can increase the pharmacokinetic parameters of TAM when coadministrated with it, especially with voriconazole. 31 Otherwise, TAM can play a synergistic action to increase the antifungal activity of other agents of azole and terbinafine. 32 The curative value of amphotericin B (AmB) and fluconazole for Cryptococcosis infection, as with Cryptococcosis meningitis, can also enhance after using with TAM.…”

Section: Tamoxifen As An Anti-fungal Drugmentioning

confidence: 99%

Tamoxifen: From Anti-cancer to Antifungal Drug

2019

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Tamoxifen (TAM) is an important drug for treatment of breast cancer. It is most effective against estrogen receptor-positive and negative breast cancer. Protective adjuvant is another applied of TAM for women at risk of development of breast cancer. Anti-cancer activity of TAM can take various pathways of action. Antagonistic with estrogen receptor and oxidation reaction are the most proposed mechanism of action of TAM in cancer cells. Recently, many studies focused on the potential antimicrobial action of TAM. Fungi are demonstrated to affect by TAM through various mechanism of action. Yeasts, especially Candida albicans, are the most common type of fungi used to test the antifungal action of TAM. Inhibitory action on some components of the calcium-calcineurin pathway in fungal cells is most acceptable mechanism of TAM action. TAM can also play a synergistic role to increase the antifungal activity of other standard agents. This review will discuss the most recent information about antifungal action of TAM.

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Use of Modeling and Simulation to Predict the Influence of Triazole Antifungal Agents on the Pharmacokinetics of Crizotinib

Chen

2022

Clinical Pharm in Drug Dev

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Crizotinib is used for the treatment of c-ros oncogene 1-positive advanced non-small-cell lung cancer. Triazole antifungal agents are widely used for invasive fungal infections in clinical practice. To predict the potential influence of different triazoles (voriconazole, fluconazole, and itraconazole) on the pharmacokinetics of crizotinib by modeling and simulation the physiologically based pharmacokinetic models were established and validated in virtual cancer subjects through Simcyp software based on the essential physicochemical properties and pharmacokinetic data collected. The validated physiologically based pharmacokinetic models were applied to predict the drug-drug interactions between crizotinib and different triazoles (voriconazole, fluconazole, or itraconazole) in patients with cancer. Crizotinib and triazole antifungal agents were administered orally. The predicted plasma concentration vs time profiles of crizotinib, voriconazole, fluconazole, and itraconazole showed good agreement with observed, respectively. The geometric mean area under the plasma concentration-time curve (AUC) of crizotinib was increased by 84%, 58%, and 79% when coadministered with voriconazole, fluconazole, or itraconazole at multiple doses, respectively. The drug-drug interaction results showed increased pharmacokinetic exposure (maximum plasma concentration and area under the plasma concentration-time curve) of crizotinib when coadministrated with different triazoles (voriconazole > itraconazole > fluconazole). Among the 3 triazoles, voriconazole exhibited the most significant influence on the pharmacokinetic exposure of crizotinib. In clinic, adverse drug reactions and toxicity related to crizotinib should be carefully monitored, and therapeutic drug monitoring for crizotinib is recommended to guide dosing and optimize treatment when coadministered with voriconazole, fluconazole, or itraconazole.

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Predicting the Effects of Different Triazole Antifungal Agents on the Pharmacokinetics of Tamoxifen

Cited by 11 publications

References 41 publications

The Influence of Different Triazole Antifungal Agents on the Pharmacokinetics of Cyclophosphamide

The Influence of Different Triazole Antifungal Agents on the Pharmacokinetics of Cyclophosphamide

Tamoxifen: From Anti-cancer to Antifungal Drug

Use of Modeling and Simulation to Predict the Influence of Triazole Antifungal Agents on the Pharmacokinetics of Crizotinib

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