Review of the Pharmacokinetics and Pharmacodynamics of Intravenous Busulfan in Paediatric Patients

Lawson, Rachael; Staatz, Christine E.; Fraser, Christopher; Hennig, Stefanie

doi:10.1007/s40262-020-00947-2

Cited by 29 publications

(50 citation statements)

References 108 publications

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“…Among the electrophilic molecules that are detoxified by GSTs are various alkylating drugs that are currently being used in the treatment of cancer. This detoxifying role, in combination with the overexpression of GSTs in several types of cancer cells, contributes to the resistance of cancer cells to alkylating agents [ 1 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 ]. This is achieved either by attenuating the efficacy of anticancer drugs or by inhibiting the mitogen-activated kinase pathway (MAP).…”

Section: Introductionmentioning

confidence: 99%

“…This is achieved either by attenuating the efficacy of anticancer drugs or by inhibiting the mitogen-activated kinase pathway (MAP). Different GST isoenzymes have been shown to be involved in these functions, such as hGSTA1-1 [ 10 , 16 , 17 ], hGSTP1-1 [ 2 , 8 , 14 ], hGSTO1-1 [ 12 ], hGSTM1-1 and hGSTM3-3 [ 15 ]. These actions are of great significance because they may compromise the efficacy and therefore the successful outcome of therapeutic approaches [ 3 , 10 , 13 ].…”

Section: Introductionmentioning

confidence: 99%

“…Different GST isoenzymes have been shown to be involved in these functions, such as hGSTA1-1 [ 10 , 16 , 17 ], hGSTP1-1 [ 2 , 8 , 14 ], hGSTO1-1 [ 12 ], hGSTM1-1 and hGSTM3-3 [ 15 ]. These actions are of great significance because they may compromise the efficacy and therefore the successful outcome of therapeutic approaches [ 3 , 10 , 13 ]. To this end, one of the strategies that are being investigated to address this problem relies on the use of specific molecules that are able to inhibit the function of GSTs [ 10 , 11 ].…”

Section: Introductionmentioning

confidence: 99%

“…These actions are of great significance because they may compromise the efficacy and therefore the successful outcome of therapeutic approaches [ 3 , 10 , 13 ]. To this end, one of the strategies that are being investigated to address this problem relies on the use of specific molecules that are able to inhibit the function of GSTs [ 10 , 11 ]. Several potent inhibitors have been developed over the last years, which are classified into two groups: those that bind to the G-site and those that bind to the H-site.…”

Section: Introductionmentioning

confidence: 99%

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The Interaction of the Flavonoid Fisetin with Human Glutathione Transferase A1-1

et al. 2021

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Glutathione transferases (GSTs) are a family of Phase II detoxification enzymes that are involved in the development of the multidrug resistance (MDR) mechanism in cancer cells and therefore affect the clinical outcome of cancer chemotherapy. The discovery of nontoxic natural compounds as inhibitors for GSTs is a promising approach for chemosensitizing and reversing MDR. Fisetin (7,3′,4′-flavon-3-ol) is a plant flavonol present in many plants and fruits. In the present work, the interaction of fisetin with human glutathione transferase A1-1 (hGSTA1-1) was investigated. Kinetic analysis revealed that fisetin is a reversible inhibitor for hGSTA1-1 with IC50 1.2 ± 0.1 μΜ. It functions as a mixed-type inhibitor toward glutathione (GSH) and as a noncompetitive inhibitor toward the electrophile substrate 1-chloro-2,4-dinitrobenzene (CDNB). In silico molecular modeling and docking predicted that fisetin binds at a distinct location, in the solvent channel of the enzyme, and occupies the entrance of the substrate-binding sites. Treatment of proliferating human epithelial colorectal adenocarcinoma cells (CaCo-2) with fisetin causes a reduction in the expression of hGSTA1-1 at the mRNA and protein levels. In addition, fisetin inhibits GST activity in CaCo-2 cell crude extract with an IC50 (2.5 ± 0.1 μΜ), comparable to that measured using purified recombinant hGSTA1-1. These actions of fisetin can provide a synergistic role toward the suppression and chemosensitization of cancer cells. The results of the present study provide insights into the development of safe and effective GST-targeted cancer chemosensitizers.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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The Interaction of the Flavonoid Fisetin with Human Glutathione Transferase A1-1

et al. 2021

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“…Lawson e colaboradores realizaram revisão da literatura sobre a farmacocinética do bussulfano em pacientes pediátricos e encontraram relação entre maiores concentrações terapêuticas do fármaco e a DVOH. Afirmam, ainda, a necessidade de monitoramento da exposição ao bussulfano durante todo o condicionamento e a necessidade de mais estudos sobre os efeitos dos metabólitos do bussulfano e de outros fatores possivelmente associados a DVOH (Lawson, Staatz &, Hennig, 2021).…”

Section: Introductionunclassified

Otimização de método analítico em HPLC-PDA para monitoração terapêutica do bussulfano oral em pacientes transplantados de células-tronco hematopoiéticas

Effting

Oliveira²,

Mundim

et al. 2021

RSD

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Otimizou-se método para monitoração plasmática de bussulfano em pacientes submetidos a transplante de células-tronco hematopoiéticas (TCTH). Utilizou-se HPLC-PDA Shimadzu, coluna C18 (150 mm x 4 mm), metanol/água/acetonitrila (65:20:15, v/v/v), fluxo 1 mL min-1; UV λ = 276 nm, tempo de análise de 17 min; derivatização com dietilcarbamato de sódio, extração com acetato de etila; curva de calibração linear de 200-5000 ng mL-1. A recuperação relativa dos controles foi de 89%±0,04 (CQA = 86%; CQM = 87%; CQB = 93%) e a do PI (padrão interno) foi de 74%±0,47. A recuperação absoluta dos controles foi de 114%±0,03 (CQA = 111%; CQM = 118%; CQB = 113%), e a do PI foi de 102%±2,5. Os limites inferiores de quantificação e detecção obtidos foram, respectivamente, de 200 ng mL-1 e 40 ng mL-1. A linearidade foi analisada pela curva de calibração (200–5000 ng.mL-1) (r = 0,998). A repetibilidade (intracorrida) foi de 1,25%-11,25%, e a precisão intermediária (intercorrida), 2,17%-10,71%. A exatidão encontrada foi de 89,61%-102,18%. A estabilidade de curta duração de amostras extraídas e das soluções foi de 6,25% e 3,18% para CQB, 7,54% e 2,4% para CQA e 13,17% e 4,13% para PI, respectivamente. A estabilidade de ciclos de congelamento e descongelamento de amostras extraídas e das soluções foi de 3,64% e 2,53% para CQB, 9,09% e 5,65% para CQA e 10,32% e 4,82% para PI, respectivamente. Desta forma, foi possível validar uma técnica para determinação do bussulfano em plasma por HPLC-PDA, adequada à monitorização terapêutica de pacientes.

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Prediction of Busulfan Clearance by Predose Plasma Metabolomic Profiling

Navarro

Baker

Risler

et al. 2022

Clin Pharma and Therapeutics

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Study HighlightsWHAT IS THE CURRENT KNOWLEDGE ON THE TOPIC?; Busulfan area under the plasma concentration-time curve (AUC) is associated with various clinical outcomes, but ~ 25% of patients achieve their target AUC with current dosing methods. Although pharmacokinetic (PK)-guided busulfan dosing reaches the target AUC in the majority of patients, it is resource-intensive and timeintensive. Thus, alternative approaches to estimate busulfan clearance are needed to achieve the target AUC with the first dose.

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Review of the Pharmacokinetics and Pharmacodynamics of Intravenous Busulfan in Paediatric Patients

Cited by 29 publications

References 108 publications

The Interaction of the Flavonoid Fisetin with Human Glutathione Transferase A1-1

The Interaction of the Flavonoid Fisetin with Human Glutathione Transferase A1-1

Otimização de método analítico em HPLC-PDA para monitoração terapêutica do bussulfano oral em pacientes transplantados de células-tronco hematopoiéticas

Prediction of Busulfan Clearance by Predose Plasma Metabolomic Profiling

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