Elevated Creatine Kinase due to Potential Drug Interaction With Ticagrelor and Atorvastatin

Beavers, Janna C.

doi:10.1177/0897190017740282

Cited by 5 publications

(2 citation statements)

References 9 publications

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“…Creatine kinase elevation and rhabdomyolysis have also been reported in clinical settings (Kido et al. 2015 ; Beavers 2019 ). Since rivaroxaban is a substrate of CYP3A4, the increased systemic exposure of rivaroxaban in our study could be explained by the inhibition effect of ticagrelor on CYP3A4.…”

Section: Discussionmentioning

confidence: 91%

Effects of ticagrelor on the pharmacokinetics of rivaroxaban in rats

Chong

Chen

Dai

et al. 2020

Pharmaceutical Biology

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Context: Rivaroxaban and ticagrelor are two common drugs for the treatment of atrial fibrillation and acute coronary syndrome. However, the drug-drug interaction between them is still unknown. Objective: To investigate the effects of ticagrelor on the pharmacokinetics of rivaroxaban in rats both in vivo and in vitro. Materials and methods: A sensitive and reliable UPLC-MS/MS method was developed for the determination of rivaroxaban in rat plasma. Ten Sprague-Dawley rats were randomly divided into ticagrelor pretreated group (10 mg/kg/day for 14 days) and control group. The pharmacokinetics of orally administered rivaroxaban (10 mg/kg, single dose) with or without ticagrelor pre-treatment was investigated with developed UPLC-MS/MS method. Additionally, Sprague-Dawley rat liver microsomes were also used to investigate the drug-drug interaction between these two drugs in vitro. Results: The C max (221.34 ± 53.33 vs. 691.18 ± 238.31 ng/mL) and the AUC (0-t) (1060.97 ± 291.21 vs. 3483.03 ± 753.83 lgÁh/L) of rivaroxaban increased significantly (p < 0.05) with ticagrelor pre-treatment. The MRT (0-1) of rivaroxaban increased from 4.41 ± 0.79 to 5.97 ± 1.11 h, while the intrinsic clearance decreased from 9.93 ± 2.55 to 2.89 ± 0.63 L/h/kg (both p < 0.05) after pre-treated with ticagrelor. Enzyme kinetic study indicated that ticagrelor decreased rivaroxaban metabolic clearance with the IC 50 value of 14.04 lmol/L. Conclusions: Our in vivo and in vitro results demonstrated that there is a drug-drug interaction between ticagrelor and rivaroxaban in rats. Further studies need to be carried out to verify whether similar interactions truly apply in humans and whether these interactions have clinical significance.

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Section: Discussionmentioning

confidence: 91%

Effects of ticagrelor on the pharmacokinetics of rivaroxaban in rats

Chong

Chen

Dai

et al. 2020

Pharmaceutical Biology

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“…Skeletal muscle damage is associated with the elevation of serum CK levels, regulation of skeletal muscle dysfunction, and fatigue [ 32 ]. Atorvastatin treatment elevates serum CK levels, leads to muscle fatigue, reduces muscular strength, and induces mitochondrial dysfunction [ 33 , 34 , 35 , 36 ]. We found that atorvastatin induced an elevation in serum CK level and fatigue index and reduced maximal forelimb strength ( Figure 1 ).…”

Section: Discussionmentioning

confidence: 99%

Exercise Training Protects against Atorvastatin-Induced Skeletal Muscle Dysfunction and Mitochondrial Dysfunction in the Skeletal Muscle of Rats

Seo

Heo

et al. 2020

JCM

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Statins are used to prevent and treat atherosclerotic cardiovascular disease, but they also induce myopathy and mitochondrial dysfunction. Here, we investigated whether exercise training prevents glucose intolerance, muscle impairment, and mitochondrial dysfunction in the skeletal muscles of Wistar rats treated with atorvastatin (5 mg kg−1 day−1) for 12 weeks. The rats were assigned to the following three groups: the control (CON), atorvastatin-treated (ATO), and ATO plus aerobic exercise training groups (ATO+EXE). The ATO+EXE group exhibited higher glucose tolerance and forelimb strength and lower creatine kinase levels than the other groups. Mitochondrial respiratory and Ca2+ retention capacity was significantly lower in the ATO group than in the other groups, but exercise training protected against atorvastatin-induced impairment in both the soleus and white gastrocnemius muscles. The mitochondrial H2O2 emission rate was relatively higher in the ATO group and lower in the ATO+EXE group, in both the soleus and white gastrocnemius muscles, than in the CON group. In the soleus muscle, the Bcl-2, SOD1, SOD2, Akt, and AMPK phosphorylation levels were significantly higher in the ATO+EXE group than in the ATO group. In the white gastrocnemius muscle, the SOD2, Akt, and AMPK phosphorylation levels were significantly higher in the ATO+EXE group than in the ATO group. Therefore, exercise training might regulate atorvastatin-induced muscle damage, muscle fatigue, and mitochondrial dysfunction in the skeletal muscles.

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Atorvastatin/ticagrelor interaction

2019

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Elevated Creatine Kinase due to Potential Drug Interaction With Ticagrelor and Atorvastatin

Abstract: A probable drug-drug interaction occurred with concomitant ticagrelor and atorvastatin. While this interaction may not always be clinically significant, it is reasonable to consider in patients who present with signs and symptoms of adverse effects.

Cited by 5 publications

References 9 publications

Effects of ticagrelor on the pharmacokinetics of rivaroxaban in rats

Effects of ticagrelor on the pharmacokinetics of rivaroxaban in rats

Exercise Training Protects against Atorvastatin-Induced Skeletal Muscle Dysfunction and Mitochondrial Dysfunction in the Skeletal Muscle of Rats

Atorvastatin/ticagrelor interaction

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