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

Cai, Tian; Liao, Youming; Chen, Zhenhua; Zhu, Yingchang; Qiu, Xincai

doi:10.1177/1060028019896894

Cited by 14 publications

(13 citation statements)

References 31 publications

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“…Cai et al investigated the influence of different triazole antifungal drugs on the pharmacokinetics of cyclophosphamide, and all tested triazoles, including ITZ, increased the pharmacokinetics of cyclophosphamide in cancer patients, as well as the area under the plasma concentration-time curve of cyclophosphamide ( Cai et al, 2020 ). Importantly, it has been reported that combination with ITZ treatment enhanced the toxicity due to chemotherapy in patients with Hodgkin’s lymphoma, causing severe myelosuppression and neurotoxicity after concurrent administration ( Bashir et al, 2006 ).…”

Section: Discussionmentioning

confidence: 99%

Induced Cell Cycle Arrest in Triple-Negative Breast Cancer by Combined Treatment of Itraconazole and Rapamycin

Fang

et al. 2022

Front. Pharmacol.

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Triple-negative breast cancer (TNBC) is the aggressive molecular type of breast carcinoma, with a high metastasis/relapse incidence and cancer-related death rate, due to lack of specific therapeutic targets in the clinic. Exploring potential therapeutic targets or developing novel therapeutic strategies are the focus of intense research to improve the survival and life quality of patients with TNBC. The current study focused on drugs targeting the mTOR signaling pathway by investigating the potential utilization of itraconazole (ITZ) combined with rapamycin in the treatment of TNBC. CCK-8, colony formation and transwell assays were conducted to evaluate the effect of ITZ with rapamycin in combination on MDA-MB-231 and BT-549 TNBC cells. Synergistic inhibition was found in terms of proliferation and motility of TNBC cells. However, apoptosis was not enhanced by the combined treatment of ITZ and rapamycin. Flow cytometry analysis showed that ITZ and/or rapamycin arrested cells in G0/G1 phase and prevented G1/S phase transition. Reduced cyclin D1 protein levels were consistent with G0/G1 phase arrest, especially when resulting from the combination of ITZ with rapamycin. In conclusion, the combination of ITZ with rapamycin is a promising therapeutic strategy for patients with TNBC through synergistically arresting cells in the G0/G1 phase of the cell cycle, rather than inducing apoptosis.

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Section: Discussionmentioning

confidence: 99%

Induced Cell Cycle Arrest in Triple-Negative Breast Cancer by Combined Treatment of Itraconazole and Rapamycin

Fang

et al. 2022

Front. Pharmacol.

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“…The essential parameters, K m and V max values of voriconazole which are listed in Table 1, were obtained from literatures 28–30,32 . The essential parameters, renal clearance, K m , and V max values of fluconazole and itraconazole which are listed in Table 1, were obtained from the SDM system and literature 21,31 . After the models were established, the accuracy of the models were verified by the observed values in published papers 34,35 .…”

Section: Methodsmentioning

confidence: 99%

“…[28][29][30]32 The essential parameters, renal clearance, K m , and V max values of fluconazole and itraconazole which are listed in Table 1, were obtained from the SDM system and literature. 21,31 After the models were established, the accuracy of the models were verified by the observed values in published papers. 34,35 The DDI model was evaluated on the basis of a study in 15 male volunteers (18-55 years of age) receiving 150 mg of crizotinib along with 200 mg of oral ketoconazole.…”

Section: Physiologically Based Pk Model Development and Verification ...mentioning

confidence: 99%

“…The establishment of PBPK models of triazoles were similar to that of crizotinib. The essential physicochemical property values [28][29][30][31][32] are listed in Table 1. The models with first-order absorption were used to characterize the absorption processes of voriconazole, fluconazole, and itraconazole.…”

Section: Physiologically Based Pk Model Development and Verification ...mentioning

confidence: 99%

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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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“…Ketoconazole had the greatest effect on the PK of cyclophosphamide among the 3 triazole antifungals. 14 Our previous research results show that posaconazole significantly increased the concentration of selinexor (a selective nuclear export inhibition) in rats, fluconazole, itraconazole, and isavuconazole have significant effects on pharmacokinetics of selinexor and increased plasma exposure of selinexor in rats. 15 , 16 …”

Section: Introductionmentioning

confidence: 94%

The Pharmacokinetic Effect of Itraconazole and Voriconazole on Ripretinib in Beagle Dogs by UPLC-MS/MS Technique

Wang¹,

Zhou²,

Su³

et al. 2021

DDDT

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Background A new UPLC-MS/MS technique for the determination of ripretinib in beagle dog plasma was developed, and the pharmacokinetic effects of voriconazole and itraconazole on ripretinib in beagle dogs were studied. Methods After extraction with ethyl acetate under alkaline conditions, ripretinib was detected using avapritinib as the internal standard (IS). The mobile phases were 0.1% formic acid-acetonitrile. The scanning method was multi-reaction monitoring using ESI+ source, and the ion pairs for ripretinib and IS were m/z 509.93→416.85 and 499.1→482.09, respectively. This animal experiment adopted a three period self-control experimental design. In the first period, ripretinib was orally administered to six beagle dogs at a dose of 5 mg/kg. In the second period, the same six beagle dogs were orally given itraconazole at a dose of 7 mg/kg, after 30 min, ripretinib was orally given. In the third period, voriconazole at a dose of 7 mg/kg was given orally, and then ripretinib was orally given. At different time points, the blood samples were collected. The concentration of ripretinib was detected, and the pharmacokinetic parameters of ripretinib were calculated. Results Ripretinib had a good linear relationship in the range of 1–1000 ng/mL. The precision, accuracy, recovery, matrix effect and stability met the requirements of the guiding principles. After erdafitinib combined with itraconazole, the C max and AUC 0→t of ripretinib increased by 38.35% and 36.36%, respectively, and the t 1/2 was prolonged to 7.53 h. After ripretinib combined with voriconazole, the C max and AUC 0→t of ripretinib increased by 37.44% and 25.52%, respectively, and the t 1/2 was prolonged to 7.33 h. Conclusion A new and reliable UPLC-MS/MS technique was fully optimized and developed to detect the concentration of ripretinib in beagle dog plasma. Itraconazole and voriconazole could inhibit the metabolism of ripretinib in beagle dogs and increase the plasma exposure of ripretinib.

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

Cited by 14 publications

References 31 publications

Induced Cell Cycle Arrest in Triple-Negative Breast Cancer by Combined Treatment of Itraconazole and Rapamycin

Induced Cell Cycle Arrest in Triple-Negative Breast Cancer by Combined Treatment of Itraconazole and Rapamycin

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

The Pharmacokinetic Effect of Itraconazole and Voriconazole on Ripretinib in Beagle Dogs by UPLC-MS/MS Technique

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