Aciphex Clinical Pharmacology

Drug Library
Aciphex - Clinical Pharmacology [Rabeprazole]

a No inferential statistics conducted for this parameter.
* (p< 0.001 versus placebo) b Gastric pH was measured every hour over a 24-hour period.

Effects on Esophageal Acid

Exposure In patients with gastroesophageal reflux disease (GERD) and moderate to severe esophageal acid exposure, ACIPHEXŽ 20 mg and 40 mg per day decreased 24-hour esophageal acid exposure. After seven days of treatment, the percentage of time that esophageal pH< 4 decreased from baselines of 24.7% for 20 mg and 23.7% for 40 mg, to 5.1% and 2.0%, respectively.

Normalization of 24-hour intraesophageal acid exposure was correlated to gastric pH> 4 for at least 35% of the 24-hour period; this level was achieved in 90% of subjects receiving ACIPHEXŽ 20 mg and in 100% of subjects receiving ACIPHEXŽ 40 mg.

With ACIPHEXŽ 20 mg and 40 mg per day, significant effects on gastric and esophageal pH were noted after one day of treatment, and more pronounced after seven days of treatment.

Effects on Serum Gastrin

In patients given daily doses of ACIPHEXŽ for up to eight weeks to treat ulcerative or erosive esophagitis and in patients treated for up to 52 weeks to prevent recurrence of disease the median fasting gastrin level increased in a dose-related manner. The group median values stayed within the normal range.

In a group of subjects treated daily with ACIPHEXŽ 20 mg for 4 weeks a doubling of mean serum gastrin concentrations were observed. Approximately 35% of these treated subjects developed serum gastrin concentrations above the upper limit of normal.

In a study of CYP2C19 genotyped subjects in Japan, poor metabolizers developed statistically significantly higher serum gastrin concentrations than extensive metabolizers.

Effects on Enterochromaffin-like (ECL) Cells

Increased serum gastrin secondary to antisecretory agents stimulates proliferation of gastric ECL cells which, over time, may result in ECL cell hyperplasia in rats and mice and gastric carcinoids in rats, especially in females (see Carcinogenesis, Mutagenesis, Impairment of Fertility).