Effects of verapamil on the pharmacokinetics of puerarin in rats

Zhou, Yun; Song, Xiaoli; Dong, Gang

doi:10.1080/00498254.2018.1518552

Cited by 16 publications

(12 citation statements)

References 28 publications

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“…Verapamil is a specific inhibitor of P-gp and CYP3A4, on which the transport and metabolism of most drugs are dependent (Srinivas 2008). Many drugs with poor oral bioavailability co-administrated with verapamil could improve their absorption (Choi and Li 2005;Huang et al 2018;Zhou et al 2019). Therefore, the interaction between HCPT and verapamil was studied in this paper to assess the effect of verapamil on the pharmacokinetics of HCPT.…”

Section: Discussionmentioning

confidence: 99%

“…The coadministration of verapamil and ibrutinib can exert severe toxicity due to the drug-drug interaction (Lambert et al 2016). Many other drugs that may be coadminstrated with verapamil in the clinic, were also reported to be influenced by verapamil, such as dihydromyricetin, puerarin, and paclitaxel (Choi and Li 2005;Huang et al 2018;Zhou et al 2019). In addition, HCPT is a substrate of P-gp and its metabolism is mainly mediated by CYP3A4 (Pu et al 2011;Burney et al 2017).…”

Section: Introductionmentioning

confidence: 99%

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Effect of verapamil on the pharmacokinetics of hydroxycamptothecin and its potential mechanism

Xing

Luo

et al. 2020

Pharmaceutical Biology

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Context: Hydroxycamptothecin (HCPT) has antitumor activity in various cancers, but its poor bioavailability and efflux limit its clinical application. Verapamil has been demonstrated to improve the bioavailability of many drugs. However, the effect of verapamil on the pharmacokinetics of HCPT was not clear. Objective: The effect of verapamil on the pharmacokinetics of HCPT was investigated to clarify the drug-drug interaction between HCPT and verapamil. Materials and methods: The pharmacokinetic profiles of oral administration of HCPT (50 mg/kg) in two group of Sprague-Dawley rats (six rats each), with pre-treatment of verapamil (10 mg/kg/day) for 7 days were investigated, with the group without verapamil pre-treatment as control. Additionally, the metabolic stability and transport of HCPT in the presence or absence of verapamil were also investigated with the employment of the rat liver microsomes and Caco-2 cell transwell model. Results: Verapamil significantly increased the peak plasma concentration (from 91.97 ± 11.30 to 125.30 ± 13.50 ng/mL), and decrease the oral clearance (from 63.85 ± 10.79 to 32.95 ± 6.17 L/h/kg). The intrinsic clearance rate was also significantly decreased (from 39.49 ± 0.42 to 28.64 ± 0.30 lL/min/mg protein) by the preincubation of verapamil. The results of Caco-2 cell transwell experiments showed the efflux of HCPT was inhibited by verapamil, as the efflux ratio decreased from 1.82 to 1.21. Discussion and conclusions: The system exposure of HCPT was increased by verapamil. Verapamil may exert this effect through inhibiting the activity of CYP3A4 or P-gp, which are related to the metabolism and transport of HCPT.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Effect of verapamil on the pharmacokinetics of hydroxycamptothecin and its potential mechanism

Xing

Luo

et al. 2020

Pharmaceutical Biology

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“…2018; Zhou et al. 2019). The control group was without the pre-treatment of verapamil before the oral administration of oridonin.…”

Section: Methodsmentioning

confidence: 99%

Influence of verapamil on the pharmacokinetics of oridonin in rats

Liu

Zhang

et al. 2019

Pharmaceutical Biology

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Context: Oridonin has been traditionally used in Chinese treatment of various cancers, but its poor bioavailability limits its therapeutic uses. Verapamil can enhance the absorption of some drugs with poor oral bioavailability. Whether verapamil can enhance the bioavailability of oridonin is still unclear. Objective: This study investigated the effect of verapamil on the pharmacokinetics of oridonin in rats and clarified its main mechanism. Materials and methods: The pharmacokinetic profiles of oral administration of oridonin (20 mg/kg) in Sprague-Dawley rats with two groups of six animals each, with or without pre-treatment of verapamil (10 mg/kg/day for 7 days) were investigated. The effects of verapamil on the transport and metabolic stability of oridonin were also investigated using Caco-2 cell transwell model and rat liver microsomes. Results: The results showed that verapamil could significantly increase the peak plasma concentration (from 146.9 ± 10.17 to 193.97 ± 10.53 ng/mL), and decrease the oral clearance (from 14.69 ± 4.42 to 8.09 ± 3.03 L/h/kg) of oridonin. The Caco-2 cell transwell experiments indicated that verapamil could decrease the efflux ratio of oridonin from 1.67 to 1.15, and the intrinsic clearance rate of oridonin was decreased by the pre-treatment with verapamil (40.06 ± 2.5 vs. 36.09 ± 3.7 mL/min/mg protein). Discussion and conclusions: These results indicated that verapamil could significantly change the pharmacokinetic profile of oridonin in rats, and it might exert these effects through increasing the absorption of oridonin by inhibiting the activity of P-gp, or through inhibiting the metabolism of oridonin in rat liver. In addition, the potential drug-drug interaction should be given special attention when verapamil is used with oridonin. Also, the dose of oridonin should be carefully selected in the clinic.

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“…Co-administered compounds which are P-gp substrates could change the activity of P-gp, thus leading to drug-drug interactions, eventually affecting the pharmacokinetics of puerarin. Single compound such as verapamil (Chen et al., 2018; Zhou et al., 2018), cyclosporine A (Su et al., 2016), menthol (Zhang et al., 2016; 2017; Yang et al., 2018) and ligustrazine (Chen et al., 2018) could decrease the efflux ratio of puerarin. Its bioenhancement is mainly due to its inhibitory activity on P-gp mediated drug efflux.…”

Section: Pharmacokinetics Of Puerarinmentioning

confidence: 99%

Pharmacokinetics and drug delivery systems for puerarin, a bioactive flavone from traditional Chinese medicine

Zhang

2019

Drug Delivery

105

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Pueraria lobata (Willd.) Ohwi is a medicinal and edible homologous plant with a long history in China. Puerarin, the main component isolated from the root of Pueraria lobata, possesses a wide range of pharmacological properties. Daidzein and glucuronides are the main metabolites of puerarin and are excreted in the urine and feces. As active substrates of P-gp, multidrug resistance-associated protein and multiple metabolic enzymes, the pharmacokinetics of puerarin can be influenced by different pathological conditions and drug-drug interactions. Due to the poor water-solubility and liposolubility, the applications of puerarin are limited. So far, only puerarin injections and eye drops are on the market. Recent years, researches on improving the bioavailability of puerarin are developing rapidly, various nanotechnologies and preparation technologies including microemulsions and SMEDDS, dendrimers, nanoparticles and nanocrystals have been researched to improve the bioavailability of puerarin. In order to achieve biocompatibility and desired activity, more effective quality evaluations of nanocarriers are required. In this review, we summarize the pharmacokinetics and drug delivery systems of puerarin up to date.

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Effects of verapamil on the pharmacokinetics of puerarin in rats

Cited by 16 publications

References 28 publications

Effect of verapamil on the pharmacokinetics of hydroxycamptothecin and its potential mechanism

Effect of verapamil on the pharmacokinetics of hydroxycamptothecin and its potential mechanism

Influence of verapamil on the pharmacokinetics of oridonin in rats

Pharmacokinetics and drug delivery systems for puerarin, a bioactive flavone from traditional Chinese medicine

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