Evaluation of CYP2C19-Mediated Pharmacokinetic Drug Interaction of Tegoprazan, Compared with Vonoprazan or Esomeprazole.
Journal
Clinical pharmacokinetics
ISSN: 1179-1926
Titre abrégé: Clin Pharmacokinet
Pays: Switzerland
ID NLM: 7606849
Informations de publication
Date de publication:
04 2023
04 2023
Historique:
accepted:
15
02
2023
medline:
12
4
2023
pubmed:
11
3
2023
entrez:
10
3
2023
Statut:
ppublish
Résumé
CYP2C19-mediated drug interactions of acid-reducing agents are clinically important given the high possibility of concomitant administration with CYP2C19 substrates. This study aimed to evaluate the effect of tegoprazan on the pharmacokinetics (PK) of a CYP2C19 substrate, proguanil, compared with vonoprazan or esomeprazole. A two-part, randomized, open-label, two-sequence, three-period crossover study was conducted in 16 healthy CYP2C19 extensive metabolizers (eight subjects per part). In each period, a single oral dose of atovaquone/proguanil 250/100 mg was administered alone or co-administered with tegoprazan 50 mg, esomeprazole 40 mg (Part 1 only) or vonoprazan 20 mg (Part 2 only). The plasma and urine concentrations of proguanil and its metabolite, cycloguanil, were measured up to 48 h post-dose. PK parameters were calculated using a non-compartmental method and compared between administered alone and co-administered with tegoprazan, vonoprazan or esomeprazole. Co-administration of tegoprazan did not significantly affect the systemic exposure of proguanil and cycloguanil. In contrast, co-administration of vonoprazan or esomeprazole increased proguanil systemic exposure and decreased cycloguanil systemic exposure, and the magnitude of the corresponding change was greater with esomeprazole co-administration than vonoprazan co-administration. Tegoprazan, unlike vonoprazan and esomeprazole, exhibited negligible CYP2C19-mediated PK interaction. It suggests that as an alternative to other acid-reducing agents, tegoprazan can be used concomitantly with CYP2C19 substrates in clinical settings. Clinicaltrials.gov identifier: NCT04568772 (Registered on September 29, 2020).
Sections du résumé
BACKGROUND AND OBJECTIVE
CYP2C19-mediated drug interactions of acid-reducing agents are clinically important given the high possibility of concomitant administration with CYP2C19 substrates. This study aimed to evaluate the effect of tegoprazan on the pharmacokinetics (PK) of a CYP2C19 substrate, proguanil, compared with vonoprazan or esomeprazole.
METHODS
A two-part, randomized, open-label, two-sequence, three-period crossover study was conducted in 16 healthy CYP2C19 extensive metabolizers (eight subjects per part). In each period, a single oral dose of atovaquone/proguanil 250/100 mg was administered alone or co-administered with tegoprazan 50 mg, esomeprazole 40 mg (Part 1 only) or vonoprazan 20 mg (Part 2 only). The plasma and urine concentrations of proguanil and its metabolite, cycloguanil, were measured up to 48 h post-dose. PK parameters were calculated using a non-compartmental method and compared between administered alone and co-administered with tegoprazan, vonoprazan or esomeprazole.
RESULTS
Co-administration of tegoprazan did not significantly affect the systemic exposure of proguanil and cycloguanil. In contrast, co-administration of vonoprazan or esomeprazole increased proguanil systemic exposure and decreased cycloguanil systemic exposure, and the magnitude of the corresponding change was greater with esomeprazole co-administration than vonoprazan co-administration.
CONCLUSION
Tegoprazan, unlike vonoprazan and esomeprazole, exhibited negligible CYP2C19-mediated PK interaction. It suggests that as an alternative to other acid-reducing agents, tegoprazan can be used concomitantly with CYP2C19 substrates in clinical settings.
TRIAL REGISTRATION
Clinicaltrials.gov identifier: NCT04568772 (Registered on September 29, 2020).
Identifiants
pubmed: 36897544
doi: 10.1007/s40262-023-01228-4
pii: 10.1007/s40262-023-01228-4
pmc: PMC10085907
doi:
Substances chimiques
1-(5-(2-fluorophenyl)-1-(pyridin-3-ylsulfonyl)-1H-pyrrol-3-yl)-N-methylmethanamine
0
Atovaquone
Y883P1Z2LT
cycloguanil
26RM326WVN
CYP2C19 protein, human
EC 1.14.14.1
Cytochrome P-450 CYP2C19
EC 1.14.14.1
Esomeprazole
N3PA6559FT
Proguanil
S61K3P7B2V
Reducing Agents
0
tegoprazan
W017G7IF4S
Banques de données
ClinicalTrials.gov
['NCT04568772']
Types de publication
Comparative Study
Journal Article
Randomized Controlled Trial
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
599-608Informations de copyright
© 2023. The Author(s).
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