Effects of Dexlansoprazole MR, a Novel Dual Delayed Release Formulation of a Proton Pump Inhibitor, on Plasma Gastrin Levels in Healthy Subjects

Abstract

Dexlansoprazole MR is a modified release formulation of a proton pump inhibitor being developed for the treatment of acid-related disorders. The purpose of this study is to characterize the plasma gastrin (PG) profile associated with administration of dexlansoprazole MR. Forty-two healthy subjects receive dexlansoprazole MR 90 mg, dexlansoprazole MR 120 mg, and lansoprazole 30 mg once daily for 5 days in a randomized, open-label, 3-period crossover study with at least 14-day washout intervals. Twenty-four-hour PG profiles are obtained at baseline (day -1 of period 1) and on days 1 and 5 in each period. Fasting PG levels are determined on days 8 and 12 in periods 1 and 2. On day 1, 24-hour PG levels increase from baseline to a similar extent with all regimens. On day 5, 24-hour PG levels with both dexlansoprazole MR regimens increase further and to a similar extent and are slightly higher than PG levels with lansoprazole. For all regimens, fasting PG levels on days 5 and 6 are higher than baseline levels (P<.05) and start to decrease by day 8, returning to near baseline at day 12. In this study, dexlansoprazole MR administration results in moderate increases in PG, similar to lansoprazole, which return to baseline levels within 7 days post dosing.

Pharmacokinetics and Safety of Dexlansoprazole MR in Adolescents With Symptomatic GERD

“…The PK, pharmacodynamic, and safety profiles of dexlansoprazole following administration of dexlansoprazole MR in adults have been studied extensively (12,14,(16)(17)(18); however, before this study, dexlansoprazole MR had not been studied in patients younger than 18 years. The course of GERD and the effects of the PPI class of drugs have been shown to be similar in adults and pediatric patients 12 to 17 years of age (3), and PPIs have been shown to be an effective treatment for GERD in both children older than 1 year and adults (5,13,19,20).…”

Helicobacter pylori eradication does not influence gastroesophageal reflux disease: a prospective, parallel, randomized, open-label, controlled trial

“…Additionally, there is no sound evidence that lansoprazole has a direct effect in LES pressure or peristalsis, apart from indirect influence due to gastrin changes, which is known to modulate LES pressure in healthy subjects (1) . Although gastrin levels were not measured, we would not expect any PPI effect one month after PPI discontinuation, since even with delayed release formulations of PPIs, gastrin levels return to baseline values within 1 week of drug discontinuation (38) . We found no correlation between gastritis pattern and LES pressures.…”

Dexansoprazole MV in the treatment of gastroesophageal reflux disease

“…Это один из вопросов безопасности длительного применения ИПП. В исследовании у здоровых добровольцев средний уровень AUC 24 гастрина увеличивался примерно в 3,5 раза по сравнению с исходными значениями после 5 дней приема декслансопразола МВ в дозах 90 или 120 мг; эта величина была сопоставимой с таковой после приема лансопразола в дозе 30 мг [31]. При проведении биопсии желудка у пациентов и излеченным эрозивным эзофагитом не было выявлено различий для любых доз декслансопразола МВ.…”