Pharmacokinetic modulation of substrate drugs via the inhibition of drug-metabolizing enzymes and transporters using pharmaceutical excipients

Choi, Min‐Koo; Lee, Jihoon; Song, Im‐Sook

doi:10.1007/s40005-022-00606-7

Cited by 5 publications

(2 citation statements)

References 95 publications

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“…Several factors might have contributed to these findings. One of the causes may be low bioavailability due to chemical degradation of phytochemicals and the intestinal/hepatic first pass [ 38 , 41 , 49 , 50 ], and plasma and liver concentrations of inhibitors may be insufficient for the IC 50 obtained in vitro CYP inhibition studies [ 51 , 52 ]. Consequently, a single oral dose of WGM did not have significant effects on the pharmacokinetics of buspirone in rats, suggesting that WGM cannot function as an inhibitor of CYP3A-mediated metabolism in vivo.…”

Section: Resultsmentioning

confidence: 99%

A High-Performance Liquid Chromatography with Photodiode Array Detection Method for Simultaneous Determination of Three Compounds Isolated from Wikstroemia ganpi: Assessment of the Effects on Cytochrome P450-Mediated Metabolism In Vitro and In Vivo

Keem,

Seo,

Kim

et al. 2023

Nutrients

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In natural products, the content and quality of the marker components differ depending on the part, production area, collection period, and extraction method; therefore, a standardized analysis method is required to obtain consistent results. This study developed a simultaneous analysis method for three marker components (7-methoxylutolin-5-O-glucoseide, pilloin 5-O-β-d-glucopyranoside, rutarensin) isolated and purified from Wikstroemia ganpi (W. ganpi). Simultaneous analysis was performed using high-performance liquid chromatography with photodiode array detection (HPLC-PDA) method that was validated according to the International Council for Harmonisation (ICH) guidelines. The developed analytical method exhibited linearity (r2 > 0.999), detection limits (0.72–3.34 μg/mL), and quantification limits (2.19–10.22 μg/mL). The relative standard deviation (RSD) value of intra- and inter-day precisions was less than 1.68%, and analyte recoveries (93.42–117.55%; RSD < 1.86%) were validated according to the analytical procedures, and all parameters were within the allowable range. Quantitative analysis of the three marker components from W. ganpi MeOH extract (WGM) showed 7-methoxylutolin-5-O-glucoseide with the highest content (51.81 mg/g). The inhibitory effects of WGM on cytochrome P450 (CYP) substrate drugs were further investigated. The in vitro study revealed that WGM inhibited the CYP3A-mediated metabolism of buspirone and that 7-methoxylutolin-5-O-glucoseide and pilloin 5-O-β-d-glucopyranoside inhibited the metabolism of buspirone with IC50 values of 2.73 and 18.7 μM, respectively. However, a single oral dose of WGM did not have significant effects on the pharmacokinetics of buspirone in rats, suggesting that WGM cannot function as an inhibitor of CYP3A-mediated metabolism in vivo.

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Section: Resultsmentioning

confidence: 99%

A High-Performance Liquid Chromatography with Photodiode Array Detection Method for Simultaneous Determination of Three Compounds Isolated from Wikstroemia ganpi: Assessment of the Effects on Cytochrome P450-Mediated Metabolism In Vitro and In Vivo

Keem,

Seo,

Kim

et al. 2023

Nutrients

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“…Moreover, PLGA can be uptaken by M cells distributed in the Peyer’s patches of the small intestinal epithelium for distribution in the lymphatic circulation. This route is crucial, as it can bypass the first-pass mechanism and P-gp-mediated efflux in the intestinal epithelium [ 159 , 160 , 161 ]. Biodegradable nanoparticles containing DOX–PLGA have been developed for treating glioblastoma and breast cancer in animal models, but they have not yet undergone clinical studies [ 162 , 163 , 164 ].…”

Section: Obstacles In and Strategies For Formulating Dox To Enhance O...mentioning

confidence: 99%

Recent Advances in Doxorubicin Formulation to Enhance Pharmacokinetics and Tumor Targeting

2023

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Doxorubicin (DOX), a widely used drug in cancer chemotherapy, induces cell death via multiple intracellular interactions, generating reactive oxygen species and DNA-adducted configurations that induce apoptosis, topoisomerase II inhibition, and histone eviction. Despite its wide therapeutic efficacy in solid tumors, DOX often induces drug resistance and cardiotoxicity. It shows limited intestinal absorption because of low paracellular permeability and P-glycoprotein (P-gp)-mediated efflux. We reviewed various parenteral DOX formulations, such as liposomes, polymeric micelles, polymeric nanoparticles, and polymer-drug conjugates, under clinical use or trials to increase its therapeutic efficacy. To improve the bioavailability of DOX in intravenous and oral cancer treatment, studies have proposed a pH- or redox-sensitive and receptor-targeted system for overcoming DOX resistance and increasing therapeutic efficacy without causing DOX-induced toxicity. Multifunctional formulations of DOX with mucoadhesiveness and increased intestinal permeability through tight-junction modulation and P-gp inhibition have also been used as orally bioavailable DOX in the preclinical stage. The increasing trends of developing oral formulations from intravenous formulations, the application of mucoadhesive technology, permeation-enhancing technology, and pharmacokinetic modulation with functional excipients might facilitate the further development of oral DOX.

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Bioanalysis of ursodeoxycholic acid and its metabolites and improved oral bioavailability using mixed micelles with poloxamer 407 and polysorbate 80

Jeon,

Lee,

Lee

et al. 2024

Biotechnol Bioproc E

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Pharmacokinetic modulation of substrate drugs via the inhibition of drug-metabolizing enzymes and transporters using pharmaceutical excipients

Cited by 5 publications

References 95 publications

A High-Performance Liquid Chromatography with Photodiode Array Detection Method for Simultaneous Determination of Three Compounds Isolated from Wikstroemia ganpi: Assessment of the Effects on Cytochrome P450-Mediated Metabolism In Vitro and In Vivo

A High-Performance Liquid Chromatography with Photodiode Array Detection Method for Simultaneous Determination of Three Compounds Isolated from Wikstroemia ganpi: Assessment of the Effects on Cytochrome P450-Mediated Metabolism In Vitro and In Vivo

Recent Advances in Doxorubicin Formulation to Enhance Pharmacokinetics and Tumor Targeting

Bioanalysis of ursodeoxycholic acid and its metabolites and improved oral bioavailability using mixed micelles with poloxamer 407 and polysorbate 80

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