Effects of HMG-CoA reductase inhibitors on the pharmacokinetics of nifedipine in rats: Possible role of P-gp and CYP3A4 inhibition by HMG-CoA reductase inhibitors

Lee, Chong-Ki; Choi, Dong‐Hyun

doi:10.1016/j.pharep.2014.08.005

Cited by 16 publications

(14 citation statements)

References 42 publications

(55 reference statements)

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“…Recently, an in vitro study has shown that simvastatin inhibited CYP3A4/5 and P-gp activity (Lee et al, 2015). An in vivo animal study performed by the same authors showed that concomitant administration of simvastatin with nifedipine, a CYP3A/5 and P-gp substrate, significantly increased the absolute bioavailability of nifedipine by 150% (Lee et al, 2015). On the other hand, atorvastatin inhibited CYP3A/5 but not P-gp activity in vitro , and had no impact on nifedipine pharmacokinetics in vivo (Lee et al, 2015).…”

Section: Discussionmentioning

confidence: 99%

“…An in vivo animal study performed by the same authors showed that concomitant administration of simvastatin with nifedipine, a CYP3A/5 and P-gp substrate, significantly increased the absolute bioavailability of nifedipine by 150% (Lee et al, 2015). On the other hand, atorvastatin inhibited CYP3A/5 but not P-gp activity in vitro , and had no impact on nifedipine pharmacokinetics in vivo (Lee et al, 2015). According to the FDA classification 1 , simvastatin would therefore be considered as a weak CYP3A/5 inhibitor (≥1.25 but <2-fold increase in AUC).…”

Section: Discussionmentioning

confidence: 99%

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Rivaroxaban-Induced Hemorrhage Associated with ABCB1 Genetic Defect

et al. 2016

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We report a patient who presented a non-ST segment elevation myocardial infarction in the context of severe normocytic hypochromic anemia related to gastrointestinal bleeding, 3 months after switching anticoagulant from the vitamin K antagonist acenocoumarol to the direct oral anticoagulant rivaroxaban. High levels of both anti-Xa activity and rivaroxaban plasma concentrations were measured despite rivaroxaban withdrawal, suggesting reduced elimination/drug clearance. Estimated half-life was 2–3 times longer than usually reported. The patient is a homozygous carrier of ABCB1 variant alleles, which could have participated to reduced elimination of rivaroxaban. Furthermore, CYP3A4/5 phenotyping showed moderately reduced enzyme activity. Drug-drug interaction with simvastatin may have contributed to decreased rivaroxaban elimination. Although in the present case moderate acute renal failure probably played a role, more clinical data are required to elucidate the impact of ABCB1 polymorphism on rivaroxaban pharmacokinetics and bleeding complications.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Rivaroxaban-Induced Hemorrhage Associated with ABCB1 Genetic Defect

et al. 2016

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“…As AC is a substrate of CYP3A4 enzymes, which is predominantly metabolized by CYP3A4 (Lee et al. 2015 ), and therefore, we infer that the herb-drug interaction between AC and DST may occur due to the effects of salvianolic acid B on the activity of CYP3A4.…”

Section: Resultsmentioning

confidence: 82%

Effects of Danshen tablets on pharmacokinetics of atorvastatin calcium in rats and its potential mechanism

Sun

Wang

Fan

et al. 2018

Pharmaceutical Biology

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Context: Danshen tablets (DST), an effective traditional Chinese multi-herbal formula, are often combined with atorvastatin calcium (AC) for treating coronary heart disease in the clinic.Objective: This study investigated the effects of DST on the pharmacokinetics of AC and the potential mechanism.Materials and methods: The pharmacokinetics of AC (1 mg/kg) with or without pretreatment of DST (100 mg/kg) were investigated using LC-MS/MS. The effects of DST (50 μg/mL) on the metabolic stability of AC were also investigated using rat liver microsome incubation systems.Results: The results indicated that Cmax (23.87 ± 4.27 vs. 38.94 ± 5.32 ng/mL), AUC(0–t) (41.01 ± 11.32 vs. 77.28 ± 12.92 ng h/mL), and t1/2 (1.91 ± 0.18 vs. 2.74 ± 0.23 h) decreased significantly (p < 0.05) when DST and AC were co-administered, which suggested that DST might influence the pharmacokinetic behavior of AC when they are co-administered. The metabolic stability (t1/2) of AC was also decreased (25.7 ± 5.2 vs. 42.5 ± 6.1) with the pretreatment of DST.Discussion and conclusions: This study indicated that the main components in DST could accelerate the metabolism of AC in rat liver microsomes and change the pharmacokinetic behaviors of AC. So these results showed that the herb-drug interaction between DST and AC might occur when they were co-administered. Therefore, the clinical dose of AC should be adjusted when DST and AC are co-administered.

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“…As ALDP is a substrate of CYP3A4 enzymes, which is predominantly metabolized by CYP3A4 (Lee et al. 2015), and therefore, we infer that the herb–drug interaction between ALDP and DST may occur due to the effects of salvianolic acid B on the activity of CYP3A4.…”

Section: Resultsmentioning

confidence: 83%

Effects of Danshen tablets on pharmacokinetics of amlodipine in rats

Zhang

Han

et al. 2019

Pharmaceutical Biology

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Context: Danshen tablets (DST), an effective traditional Chinese multi-herbal formula, are often combined with amlodipine (ALDP) for treating coronary heart disease. Objective: This study investigated the effects of DST on the pharmacokinetics of ALDP and the potential mechanism. Materials and methods: The pharmacokinetics of ALDP (1 mg/kg) in male Sprague–Dawley rats ( n = 6), with or without pretreatment of DST (100 mg/kg for 7 d), were investigated using LC-MS/MS. The effects of DST on the metabolic stability of ALDP were also investigated using rat liver microsomes (RLM). Results: The results indicated that C max (16.25 ± 2.65 vs. 22.79 ± 2.35 ng/ml), AUC (0– t ) (222.87 ± 59.95 vs. 468.32 ± 69.87 n gh/ml), and t 1/2 (10.60 ± 1.05 vs. 14.15 ± 1.59 h) decreased significantly when DST and ALDP were co-administered, which suggested that DST might influence the pharmacokinetic behaviour of ALDP when they are co-administered. The metabolic stability of ALDP was also decreased (23.6 ± 4.7 vs. 38.9 ± 5.2) with the pretreatment of DST. Discussion and conclusions: This study indicated that DST could accelerate the metabolism of ALDP in RLM and change the pharmacokinetic behaviours of ALDP. Accordingly, these results showed that the herb–drug interaction between DST and ALDP might occur when they were co-administered. Therefore, the clinical dose of ALDP should be increased when DST and ALDP are co-administered.

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Effects of HMG-CoA reductase inhibitors on the pharmacokinetics of nifedipine in rats: Possible role of P-gp and CYP3A4 inhibition by HMG-CoA reductase inhibitors

Abstract: The increased bioavailability of nifedipine may be mainly due to inhibition of both P-gp in the small intestine and CYP3A subfamily-mediated metabolism of nifedipine in the small intestine and/or in the liver and to the reduction of the CL/F of nifedipine by fluvastatin and simvastatin.

Cited by 16 publications

References 42 publications

Rivaroxaban-Induced Hemorrhage Associated with ABCB1 Genetic Defect

Rivaroxaban-Induced Hemorrhage Associated with ABCB1 Genetic Defect

Effects of Danshen tablets on pharmacokinetics of atorvastatin calcium in rats and its potential mechanism

Effects of Danshen tablets on pharmacokinetics of amlodipine in rats

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