Pharmacokinetics and Pharmacodynamics of YYD601, a Dual Delayed-Release Formulation of Esomeprazole, Following Single and Multiple Doses in Healthy Adult Volunteers Under Fasting and Fed Conditions

Hae Won Lee, Woo Youl Kang, Wookjae Jung, Mi-Ri Gwon, Kyunghee Cho, Young-Ran Yoon, Sook Jin Seong, Hae Won Lee, Woo Youl Kang, Wookjae Jung, Mi-Ri Gwon, Kyunghee Cho, Young-Ran Yoon, Sook Jin Seong

Abstract

Background: YYD601 was developed as a novel dual delayed release (DDR) formulation of esomeprazole to prolong the plasma esomeprazole concentration and extend the duration of acid suppression.

Purpose: The pharmacokinetic (PK) and pharmacodynamics (PD) characteristics of YYD601 after single and multiple oral administrations were investigated in healthy Korean adults under fasting and fed conditions, and compared with the original esomeprazole capsule.

Methods: In the single-center, randomized, open-label, parallel-design, two-period study, thirty two volunteers were enrolled into four dosing groups, including esomeprazole 40-mg (group A), YYD60130-mg (group B), YYD601 40-mg (group C), and YYD601 60-mg (group D) once daily for 5 days. Blood samples were collected for PK analysis, before and up to 24 h after dosing. For PD characteristics of YYD601, the percentages of time with intragastric pH > 4 over a 24-h period and during night-time following multiple oral administrations were evaluated.

Results: A total of 27 subjects completed the study. YYD601 showed a dual-peak PK profile under fasting condition, with delayed Tmax, compared with conventional formulation. There were no significant differences in the AUC values adjusted for dose between the three YYD601 dosage groups and the conventional esomeprazole 40 mg. The esomeprazole AUC following single and multiple administration decreased with food intake by approximately 33%. YYD601 showed a linear pharmacokinetic profile in the dose range studied. There was no statistically significant difference in increase in mean percentage of time with intragastric pH > 4 for 24-hour and during night-time between the three different doses of YYD601 and the conventional formulation. The treatments were well-tolerated during the study and no serious adverse events were observed.

Conclusion: YYD601 30 mg has a comparable effect on gastric acid inhibition as conventional esomeprazole 40 mg following once daily oral administration. Single and multiple oral dosing of YYD601 up to 60 mg were safe and well-tolerated throughout the study.

Clinical trial registry: https://ichgcp.net/clinical-trials-registry/NCT03558477" title="See in ClinicalTrials.gov">NCT03558477 (date of registration: June 15, 2018; study period: between October 2017 and February 2018).

Keywords: dual delayed release; esomeprazole; pharmacodynamics; pharmacokinetics.

Conflict of interest statement

Kyunghee Cho is an employee of Biocore Co. Ltd. The authors report no conflicts of interest regarding this work or the content of this article.

© 2022 Lee et al.

Figures

Figure 1
Figure 1
Study design. In period 1, the subjects were administered the study drugs after overnight fasting for 5 days. After a 7-day washout, subjects were administered the same study drugs following a high-fat meal for 5 days.
Figure 2
Figure 2
The subject disposition for study screening, enrollment, dosing, and follow-up. Flow diagram illustrating subjects enrolled in the study. Subjects (n = 30) were randomized to one of the four groups.
Figure 3
Figure 3
Mean (SD) plasma concentration-time profiles of esomeprazole on day 1 after a single administration and on day 5 after multiple administrations, in fasting condition (A) and in fed conditions (B).
Figure 4
Figure 4
Mean plasma concentration-time profiles of esomeprazole under fasting and fed conditions after single (A) and multiple (B) oral administration of YYD601 40 mg, and after single (C) and multiple (D) administration of 40-mg esomeprazole.
Figure 5
Figure 5
Mean intragastric pH measurements over a 24-h interval at baseline and with 30, 40, and 60-mg YYD601 and 40-mg esomeprazole in healthy subjects after 5-day multiple administrations in fasting condition, to depict the sequential time course of intragastric pH recorded in the study. On the 24-h scale, the x-axis shows 0h (hour 8:00 on day 5 to 24h (hour 8:00 on day six).
Figure 6
Figure 6
The representative individual plasma concentration-time profile of esomeprazole obtained from one subject following single and multiple administrations of YYD601 40 mg (A) and that obtained from another subject administered with esomeprazole 40 mg (B).

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