Blood concentrations of tacrolimus upon conversion from rabeprazole to vonoprazan in renal transplant recipients: Correlation with cytochrome P450 gene polymorphisms

Watari, Shogo; Araki, Motoo; Matsumoto, Jun; Yoshinaga, Kasumi; Sekito, Takanori; Maruyama, Yuki; Mitsui, Yosuke; Sadahira, Takuya; Kubota, Risa; Nishimura, Satoshi; Wada, Koichiro; Kobayashi, Yasuyuki; Takeuchi, Hidemi; Tanabe, Katsuyuki; Kitagawa, Masashi; Morinaga, Hiroshi; Kitamura, Shinji; Sugiyama, Hitoshi; Ariyoshi, Noritaka; Wada, Jun; Watanabe, Masami; Watanabe, Tetsu; Nasu, Yasutomo

doi:10.1016/j.dmpk.2021.100407

Cited by 3 publications

(4 citation statements)

References 16 publications

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“…Vonoprazan coadministration showed a slightly higher percentage increase of the C/D ratio in CYP3A5*1-carriers compared with noncarriers (44.4% vs. 39.1%), though not statistically significant. A similar result was reported in another study employing outpatients where switching to vonoprazan provided no significant increase of tacrolimus trough levels, even in the CYP2C19 IM/PM in the CYP3A5*1 noncarriers [30].…”

Section: Discussionsupporting

confidence: 88%

“…This may be a potential bias for the study setting. The increase in C/D ratio of tacrolimus after switching of rabeprazole to vonoprazan was large (41.8%) compared with previous studies by Mei T. [27] and Watari S. [30], which showed a 10.6% increase and no increase after the conversion, respectively, in the outpatient phase of posttransplantation. To confirm this difference, the data for a larger number of the patients is required in the early phase of post-transplantation.…”

Section: Discussioncontrasting

confidence: 54%

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Drug–Drug Interaction between Tacrolimus and Vonoprazan in Kidney Transplant Recipients

Suzuki

Yoshihashi

Takahashi

et al. 2021

JCM

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Kidney transplant recipients with tacrolimus-based immunosuppressive therapy are often treated with proton-pump inhibitors (PPIs) to prevent gastric ulcer complications. Vonoprazan, a potassium-competitive acid blocker, is a novel PPI possessing different metabolic pathways from conventional PPIs (e.g., omeprazole, lansoprazole and rabeprazole). However, no data are available on the change in blood concentration of tacrolimus after switching rabeprazole, a conventional PPI, to vonoprazan coadministration in the initial period of post-transplantation. This is a retrospective study of 18 kidney transplant recipients. The blood concentration and the concentration to dose (C/D) ratio of tacrolimus were compared before and after switching from rabeprazole to vonoprazan. Impacts of CYP2C19 and CYP3A5 genetic polymorphisms on the drug–drug interaction were also examined. The median (range) trough concentration of tacrolimus was significantly increased from 5.2 (3.6–7.4) to 8.1 (6.1–11.7) ng/mL (p < 0.0005) after switching from rabeprazole to vonoprazan. The C/D ratio of tacrolimus was also significantly increased from 38.1 (16.5–138.1) to 48.9 (26.2–207.2) (p < 0.0005). The percent changes of tacrolimus concentrations and C/D were 65.8% and 41.8%, respectively. CYP2C19 and CYP3A5 genetic polymorphisms did not affect the change in concentration and C/D ratio of tacrolimus. The present study indicates that vonoprazan coadministration increases the tacrolimus concentration regardless of CYP2C19 or CYP3A5 genetic polymorphisms. Thus, frequent monitoring of blood tacrolimus concentration is required when vonoprazan is introduced as an intensive gastric acid blocker in the early phase of post-transplantation.

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Section: Discussionsupporting

confidence: 88%

Section: Discussioncontrasting

confidence: 54%

Drug–Drug Interaction between Tacrolimus and Vonoprazan in Kidney Transplant Recipients

Suzuki

Yoshihashi

Takahashi

et al. 2021

JCM

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“…34 Vonoprazan's metabolism, mainly involving the hepatic microsomal enzyme CYP3A4 and unaffected by the CYP2C19 gene polymorphism, ensures a robust acid-suppressive effect even in individuals with the CYP2C19 fast metabolizing genotype. 35,36 The current primary dosing regimen for HDDT (20 mg of esomeprazole qid and 1000 mg of amoxicillin tid for 14 days) 24 and the 14-day dual therapy with vonoprazan and amoxicillin (20 mg of vonoprazan bid and 750 mg of amoxicillin qid for 14 days), 26,37 still presents certain limitations. Esomeprazole and vonoprazan, administered at varying doses and treatment durations, exhibit distinct safety and efficacy profiles.…”

Section: Discussionmentioning

confidence: 99%

“…Another meta‐analysis comparing the efficacy and safety of vonoprazan‐based versus PPI‐based triple therapy for H. pylori eradication has revealed a significantly reduced incidence of adverse effects and high tolerability 34 . Vonoprazan's metabolism, mainly involving the hepatic microsomal enzyme CYP3A4 and unaffected by the CYP2C19 gene polymorphism, ensures a robust acid‐suppressive effect even in individuals with the CYP2C19 fast metabolizing genotype 35,36 …”

Section: Discussionmentioning

confidence: 99%

Clinical Study on the Eradication of Helicobacter pylori by Vonoprazan Combined with Amoxicillin for 10‐Day Dual Therapy

Yan,

Dai,

et al. 2024

Clinical Pharm in Drug Dev

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Vonoprazan holds significant research promise for Helicobacter pylori eradication, with the goal of determining the most effective drug regimen. In this study, H. pylori patients (426) were enrolled and randomized into 3 groups: an EA14 group (20 mg of esomeprazole qid and 1000 mg of amoxicillin tid for 14 days), a VA14 group (20 mg of vonoprazan bid and 750 mg of amoxicillin qid for 14 days), and a VA10 group (20 mg of vonoprazan bid and 1000 mg of amoxicillin tid for 10 days). Key outcomes encompassed the H. pylori eradication rate, patient adverse effects, and compliance. In the EA14, VA14, and VA10 groups, H. pylori eradication rates were 89.4%, 90.1%, and 88.7% in intention‐to‐treat analysis, and 94.2%, 94.4%, and 94.6% in per‐protocol analysis, respectively. Adverse events incidences were 14.8%, 12.7%, and 5.6%, while compliance rates were 88.7%, 90.9%, and 95.8%, respectively. Notably, the VA10 regimen demonstrated comparable H. pylori eradication rates, adverse effect incidences, and compliance levels to the EA14 and VA14 regimens.

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The Effects of Vonoprazan Fumarate on the Tacrolimus Blood Concentration in Liver Transplant Recipients

Hidaka¹,

Soyama²,

HASHIZUME³

et al. 2022

CDP

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Background/Aim: The proton pump inhibitors were reported to affect the blood concentration of tacrolimus. Vonoprazan fumarate is a new acid suppressant with potent acid inhibitory effects. There have been no reports concerning the effect of vonoprazan on the tacrolimus blood concentration in liver transplant (LT) recipients. Patients and Methods: Eighteen living donor liver transplantation (LDLT) recipients who switched from proton pump inhibitors (PPIs) to vonoprazan between 2016 to 2018 were enrolled in this retrospective study. We investigated blood levels of tacrolimus, and liver and renal function before and after the change from PPIs to vonoprazan. Results: The median C0/D of tacrolimus before conversion, 3 months after conversion, and 6 months after conversion were 2.33, 1.53, and 1.89, respectively, and there was no significant difference. Conversion from another PPI to vonoprazan was not associated with a worsening liver function. The estimated glomerular filtration rate was significantly worse after conversion. Conclusion: Vonoprazan can be safely administered to LT recipients receiving tacrolimus during the stable period.

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Blood concentrations of tacrolimus upon conversion from rabeprazole to vonoprazan in renal transplant recipients: Correlation with cytochrome P450 gene polymorphisms

Cited by 3 publications

References 16 publications

Drug–Drug Interaction between Tacrolimus and Vonoprazan in Kidney Transplant Recipients

Drug–Drug Interaction between Tacrolimus and Vonoprazan in Kidney Transplant Recipients

Clinical Study on the Eradication of Helicobacter pylori by Vonoprazan Combined with Amoxicillin for 10‐Day Dual Therapy

The Effects of Vonoprazan Fumarate on the Tacrolimus Blood Concentration in Liver Transplant Recipients

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