What is the clinical evidence from this study?

Study design: Other. Population: Healthy rats (n=10). Intervention: Vonoprazan vs. 0.5% CMC-Na. Primary outcome: Pharmacokinetic parameters of cytochrome P450 probe drugs (p=<0.05).

February 14, 2020Frontiers in PharmacologyOpen Access

Cytochrome P450-Based Drug-Drug Interactions of Vonoprazan In Vitro and In Vivo

Q: What are the key findings of this study?

Vonoprazan significantly inhibited the metabolism of midazolam, bupropion, dextromethorphan, and tolbutamide in rats, indicating inhibitory effects on CYP3A4, CYP2B6, CYP2D6, and CYP2C9.

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Key result

Vonoprazan significantly inhibited the metabolism of midazolam, bupropion, dextromethorphan, and tolbutamide in rats, indicating inhibitory effects on CYP3A4, CYP2B6, CYP2D6, and CYP2C9.

Why the study?

As a potential alternative to proton-pump inhibitors, determining the cytochrome P450-based drug-drug interactions of vonoprazan was vital for further clinical applications.

Population

Rat liver microsomes and rats

Comparison

Vonoprazan administration vs no vonoprazan administration

Design

In vitro and in vivo animal study

Authors

YWYiran WangUniversity of California, San Francisco CWChangxiong WangZhejiang Chinese Medical University SWShuanghu WangLishui Central Hospital

Discussion

Member takes

Implication

May warrant caution with CYP substrates in polypharmacy; rat data leaves human relevance open.

Structured PICO

Population

10 male Sprague-Dawley rats were used to evaluate the in vivo pharmacokinetic effects of vonoprazan on cytochrome P450 probe drugs.

Intervention

Vonoprazan 5 mg/kg administered via gavage for 14 days (in vivo) and 1-100 mM (in vitro).

Comparator

0.5% carboxy methyl cellulose sodium (CMC-Na) administered for 14 days (in vivo).

Outcome

Inhibition of cytochrome P450 enzymes measured by IC50 values (in vitro) and pharmacokinetic parameters including AUC, Cmax, Tmax, and CLz/F of probe drugs (in vivo).surrogate

Main Result

p-value: p=<0.05

Vonoprazan inhibits CYP3A4, CYP2C9, CYP2D6, and CYP2B6 in rat models, indicating a potential for significant drug-drug interactions when coadministered with substrates of these enzymes.

Limitations

Rats do not have CYP2C19, limiting the evaluation of this specific enzyme.
The study was conducted in animal models and in vitro, requiring further clinical trials in humans to confirm the findings.
Rats do not have CYP2C19, limiting translation to humans
Not yet applied to human beings in this study

Cite This Study

Wang et al. (2020) studied Healthy rats (n=10). Vonoprazan vs. 0.5% CMC-Na was evaluated on Pharmacokinetic parameters of cytochrome P450 probe drugs (p=<0.05). Vonoprazan significantly inhibited the metabolism of midazolam, bupropion, dextromethorphan, and tolbutamide in rats, indicating inhibitory effects on CYP3A4, CYP2B6, CYP2D6, and CYP2C9.

synapsesocial.com/papers/6a98db2b41c8c9d4aef0c05f https://doi.org/10.3389/fphar.2020.00053

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February 14, 2020Frontiers in PharmacologyOpen Access

Cytochrome P450-Based Drug-Drug Interactions of Vonoprazan In Vitro and In Vivo

View Full Paper

Ask AI

Bookmark

Key result

Vonoprazan significantly inhibited the metabolism of midazolam, bupropion, dextromethorphan, and tolbutamide in rats, indicating inhibitory effects on CYP3A4, CYP2B6, CYP2D6, and CYP2C9.

Why the study?

As a potential alternative to proton-pump inhibitors, determining the cytochrome P450-based drug-drug interactions of vonoprazan was vital for further clinical applications.

Population

Rat liver microsomes and rats

Comparison

Vonoprazan administration vs no vonoprazan administration

Design

In vitro and in vivo animal study

Authors

YWYiran WangUniversity of California, San Francisco CWChangxiong WangZhejiang Chinese Medical University SWShuanghu WangLishui Central Hospital

Discussion

Member takes

Implication

May warrant caution with CYP substrates in polypharmacy; rat data leaves human relevance open.

Structured PICO

Population

10 male Sprague-Dawley rats were used to evaluate the in vivo pharmacokinetic effects of vonoprazan on cytochrome P450 probe drugs.

Intervention

Vonoprazan 5 mg/kg administered via gavage for 14 days (in vivo) and 1-100 mM (in vitro).

Comparator

0.5% carboxy methyl cellulose sodium (CMC-Na) administered for 14 days (in vivo).

Outcome

Inhibition of cytochrome P450 enzymes measured by IC50 values (in vitro) and pharmacokinetic parameters including AUC, Cmax, Tmax, and CLz/F of probe drugs (in vivo).surrogate

Main Result

p-value: p=<0.05

Vonoprazan inhibits CYP3A4, CYP2C9, CYP2D6, and CYP2B6 in rat models, indicating a potential for significant drug-drug interactions when coadministered with substrates of these enzymes.

Limitations

Rats do not have CYP2C19, limiting the evaluation of this specific enzyme.
The study was conducted in animal models and in vitro, requiring further clinical trials in humans to confirm the findings.
Rats do not have CYP2C19, limiting translation to humans
Not yet applied to human beings in this study

Cite This Study

synapsesocial.com/papers/6a98db2b41c8c9d4aef0c05f https://doi.org/10.3389/fphar.2020.00053

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