Influences of ABC transporter and CYP3A4/5 genetic polymorphisms on the pharmacokinetics of lenvatinib in Chinese healthy subjects

Li, Jiaming; Wang, Xiaoqian; Chen, Ning; Wang, Zhao-Yu; Wang, Yao; Zheng, Ming; Zhang, Siliang; Lu, Yang; Zhang, Yongjie; Li, Ning; Chen, Xijing; Zhao, Di

doi:10.1007/s00228-020-02879-z

Cited by 13 publications

(9 citation statements)

References 35 publications

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“…Exclusion criteria were as follows: (1) had severe heart, liver, kidney, and other organic diseases; (2) drug contraindications or drug allergy; (3) diabetes, hypertension, history of chronic pain, or use of analgesic drugs; (4) drugs that affected the CYP3A enzyme activity were taken within 1 month before surgery; (5) patients with disturbance of consciousness or mental disorders, depression, or anxiety and could not cooperate with the treatment; and (6) cases with incomplete information. This study was approved by the medical ethics committee of the Affiliated Hospital of Youjiang Medical University for Nationalities (approval no.…”

Section: Study Subjectsmentioning

confidence: 99%

“…Previous studies have demonstrated that SNPs could lead to individualized differences in analgesic effects by affecting the pharmacokinetics of sufentanil [ 3 ]. Cytochrome P450 (CYP) 3A4 was shown to be responsible for sufentanil N-dealkylation and generation of norfentanyl, but significant differences were observed in CYP3A4 enzyme activity in different individuals [ 4 ], which may have been related to genetic factors [ 5 ].…”

Section: Introductionmentioning

confidence: 99%

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Significance of CYP3A4 $*$ 1G and OPRM1 A118G Polymorphisms in Postoperative Sufentanil Analgesia in Women of Different Ethnicities

Zhang

Zheng

Pan

et al. 2022

Computational and Mathematical Methods in Medicine

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Objective. To investigate the association between CYP3A4 ∗ 1G and OPRM1A118G gene polymorphisms and postoperative analgesia with sufentanil in women of Zhuang ethnicity from western Guangxi, China. Methods. Forty-eight Chinese Zhuang women who underwent elective myomectomy under general anesthesia in our hospital from January 2019 to December 2020 were selected, and another 47 Chinese Han patients in the same period were selected as the control subjects. CYP3A4 ∗ 1G and OPRM1 A118G gene polymorphisms as well as sedation and pain scores at different time points after surgery were compared between the two groups of patients to analyze the relationship between the degree of pain and dosage of sufentanil and to analyze the effect of gene polymorphisms on the occurrence of adverse reactions. Results. The frequencies of ∗ 1/ ∗ 1G and ∗ 1G/ ∗ 1G genotypes, allele 1 ∗ G of CYP3A4 ∗ 1G and genotypes AA, and allele A of OPRM1 A118G in Zhuang patients were lower than those in Han patients, while the frequencies of ∗ 1/ ∗ 1, allele ∗ 1 of CYP3A4 ∗ 1G and genotypes AG, genotypes GG, and allele G of OPRM1 A118G were higher in Zhuang women. There was no significant difference in the Ramsay and VAS scores between the two groups at different time points after surgery, but the sufentanil use in Zhuang patients was higher than in Han patients at different time points after surgery. In addition, sufentanil use was highest in Zhuang patients with the ∗ 1/ ∗ 1 genotype of the CYP3A4 ∗ 1G gene. No significant difference was found in the incidence of adverse reactions during analgesia between the two groups. Conclusion. CYP3A4 ∗ 1G could be associated with postoperative sufentanil analgesia in Zhuang patients in western Guangxi and should be considered when developing personalized analgesia regimens.

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Section: Study Subjectsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Significance of CYP3A4 $*$ 1G and OPRM1 A118G Polymorphisms in Postoperative Sufentanil Analgesia in Women of Different Ethnicities

Zhang

Zheng

Pan

et al. 2022

Computational and Mathematical Methods in Medicine

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“…This suggests that most severe AE occur early in the course of treatment, and if managed patients may be continued on the medication for a prolonged period of time (61,62). There is also some data that may demonstrate some of Japanese or Chinese decent may have a higher percentage of polymorphisms in specific transporters involved in the clearance of lenvatinib (110,111) and therefore they potentially have higher blood concentrations and greater toxicity at a given dose. Other side effects may be worse in certain ethnicities, for example pazopanib associated hypopigmentation in those with dark skin tones (112).…”

Section: Side Effectsmentioning

confidence: 99%

Novel Therapeutics in Radioactive Iodine-Resistant Thyroid Cancer

2021

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Iodine-resistant cancers account for the vast majority of thyroid related mortality and, until recently, there were limited therapeutic options. However, over the last decade our understanding of the molecular foundation of thyroid function and carcinogenesis has driven the development of many novel therapeutics. These include FDA approved tyrosine kinase inhibitors and small molecular inhibitors of VEGFR, BRAF, MEK, NTRK and RET, which collectively have significantly changed the prognostic outlook for this patient population. Some therapeutics can re-sensitize de-differentiated cancers to iodine, allowing for radioactive iodine treatment and improved disease control. Remarkably, there is now an FDA approved treatment for BRAF-mutated patients with anaplastic thyroid cancer, previously considered invariably and rapidly fatal. The treatment landscape for iodine-resistant thyroid cancer is changing rapidly with many new targets, therapeutics, clinical trials, and approved treatments. We provide an up-to-date review of novel therapeutic options in the treatment of iodine-resistant thyroid cancer.

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“…Therefore, LEN and TEL are likely to be used in combination in clinical settings due to the high incidence of hypertension induced by LEN and the unique pharmacological properties of TEL. In vitro studies have shown that TEL is the substrate and inhibitor of P-glycoprotein (P-gp), breast cancer resistance protein (BCRP), and multidrug resistance-associated protein 2 (MRP2) [21,22]; similarly, LEN is a substrate for P-gp, and BCRP [23,24]. Thus, there may be drug-drug interactions based on transporters when LEN is administered in combination with TEL.…”

Section: Introductionmentioning

confidence: 99%

A Simple UPLC/MS-MS Method for Simultaneous Determination of Lenvatinib and Telmisartan in Rat Plasma, and Its Application to Pharmacokinetic Drug-Drug Interaction Study

Cui¹,

Xiao

et al. 2022

Molecules

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Lenvatinib is a multi-targeted tyrosine kinase inhibitor that inhibits tumor angiogenesis, but hypertension is the most common adverse reaction. Telmisartan is an angiotensin receptor blocker used to treat hypertension. In this study, a simple ultra-performance liquid chromatography-tandem mass spectrometry method was developed for the simultaneous determination of lenvatinib and telmisartan, and it was applied to the pharmacokinetic drug interaction study. Plasma samples were treated with acetonitrile to precipitate protein. Water (containing 5 mM of ammonium acetate and 0.1% formic acid) and acetonitrile (0.1% formic acid) were used as the mobile phases to separate the analytes with gradient elution using a column XSelect HSS T3 (2.1 mm × 100 mm, 2.5 μm). Multiple reaction monitoring in the positive ion mode was used for quantification. The method was validated and the precision, accuracy, matrix effect, recovery, and stability of this method were reasonable. The determination of analytes was not interfered with by other substances in the blank plasma, and the calibration curves of lenvatinib and telmisartan were linear within the range of 0.2–1000 ng/mL and 0.1–500 ng/mL, respectively. The results indicate that lenvatinib decreased the systemic exposure of telmisartan. Potential drug interactions were observed between lenvatinib and telmisartan.

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Influences of ABC transporter and CYP3A4/5 genetic polymorphisms on the pharmacokinetics of lenvatinib in Chinese healthy subjects

Cited by 13 publications

References 35 publications

Significance of CYP3A4 $*$ 1G and OPRM1 A118G Polymorphisms in Postoperative Sufentanil Analgesia in Women of Different Ethnicities

Significance of CYP3A4 $*$ 1G and OPRM1 A118G Polymorphisms in Postoperative Sufentanil Analgesia in Women of Different Ethnicities

Novel Therapeutics in Radioactive Iodine-Resistant Thyroid Cancer

A Simple UPLC/MS-MS Method for Simultaneous Determination of Lenvatinib and Telmisartan in Rat Plasma, and Its Application to Pharmacokinetic Drug-Drug Interaction Study

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Influences of ABC transporter and CYP3A4/5 genetic polymorphisms on the pharmacokinetics of lenvatinib in Chinese healthy subjects

Cited by 13 publications

References 35 publications

Significance of CYP3A4 ∗ 1G and OPRM1 A118G Polymorphisms in Postoperative Sufentanil Analgesia in Women of Different Ethnicities

Significance of CYP3A4 ∗ 1G and OPRM1 A118G Polymorphisms in Postoperative Sufentanil Analgesia in Women of Different Ethnicities

Novel Therapeutics in Radioactive Iodine-Resistant Thyroid Cancer

A Simple UPLC/MS-MS Method for Simultaneous Determination of Lenvatinib and Telmisartan in Rat Plasma, and Its Application to Pharmacokinetic Drug-Drug Interaction Study

Contact Info

Product

Resources

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Significance of CYP3A4 $*$ 1G and OPRM1 A118G Polymorphisms in Postoperative Sufentanil Analgesia in Women of Different Ethnicities

Significance of CYP3A4 $*$ 1G and OPRM1 A118G Polymorphisms in Postoperative Sufentanil Analgesia in Women of Different Ethnicities