Drug Safety Evaluation

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Rabeprazole: a pharmacologic
and clinical review for
acid-related disorders
1.

Introduction

Alia Dadabhai & Frank K Friedenberg

2.

Pharmacology

3.

Drug safety

Temple University School of Medicine, Gastroenterology Section, Parkinson Pavilion, 8th Floor,
3401 North Broad Street, PA 19140, Philadelphia, USA

4.

Adverse events

5.

Laboratory abnormalities

6.

Combination treatment with

amoxicillin and clarithromycin
for H. pylori

7.

Post-marketing adverse events

8.

Expert opinion

Rabeprazole is a proton pump inhibitor that can be used in the treatment

of acid-peptic-related disorders (gastroesophageal reflux disease [GERD],
duodenal ulcer, gastric ulcer, gastric acid hypersecretory syndromes) and
Helicobacter pylori. Pharmacodynamic data has demonstrated that
rabeprazole, with a high pKa of 5.0, can be activated at a higher pH than
other proton pump inhibitors. This possibly results in faster onset of action.
Owing to its non-enzymatic pathway of metabolism, rabeprazole is also less
influenced by genetic polymorphisms of the CYP2C19, which others proton
pump inhibitors are dependent on. In a 2-week, placebo-controlled trial,
rabeprazole was both rapid and effective in relieving heartburn on day 1 of
therapy and improved other GERD-related symptoms including regurgitation,
belching, bloating, early satiety and nausea. For oesophageal reflux disease
without erosions both 10 and 20 mg of rabeprazole are equivalent and better
than placebo at 2 and 4 weeks. An on-demand approach to non-erosive
reflux disease with 10 mg of rabeprazole has also been documented as
superior to placebo. Some success in the treatment of extra-oesophageal
manifestations of GERD, such as asthma and chronic laryngitis, has also
been achieved with rabeprazole. Overall, rabeprazole with very few side
effects is a safe and efficacious medication for acid suppression therapy.
Keywords: acid-related disorders, proton pump inhibitors, rabeprazole
Expert Opin. Drug Saf. (2009) 8(1):119-126

1.

Introduction

Rabeprazole is a drug in the class of proton pump inhibitors (PPIs), which

covalently binds and renders the gastric parietal cell proton pump inactive.
Suppression of H+/K+-ATPase activity increases the gastric pH. Proton pump
inhibitors are used in the management of active duodenal ulcers, gastric ulcers,
gastroesophageal reflux disease (GERD) and pathological hypersecretory syndromes
(such as ZollingerEllison syndrome, multiple endocrine adenomas and systemic
mastocytosis). Proton pump inhibitors are also used in association with antibiotics
in the eradication of Helicobacter pylori. The purpose of this review is to compare
the clinical efficacy of rabeprazole (Aciphex, Eisai Company Ltd, Tokyo, Japan)
with other PPIs on the basis of trials that have investigated this medication.
2.

Pharmacology

2.1

Pharmacodynamics

Inhibition of proton pump enzymes is an effective way to increase the gastric

luminal pH. All PPIs accomplish this by concentrating in the secretory canaliculus
of the parietal cell (Figure 1). The PPIs available at present are substituted
benzimidazoles that undergo a conversion to an active sulphonamide compound
10.1517/14740330802622892 2009 Informa UK Ltd ISSN 1474-0338
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119

Rabeprazole

Histamine H2
receptor antagonists

Acetylcholine
Muscarinic
antagonists

Muscarinic
M3 receptor

Gastrin
Histamine
Histamine H2 receptor

CCK2 receptor
Ca2+dependent
pathway

cAMPdependent
pathway
+

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H+
Parietal
cell

K+
+ +

H K -ATPase

Rabeprazole

CI-

Acid (HCI)

Gastric gland
lumen

Figure 1. Model demonstrating rabeprazoles site of action at proton pump. Gastric acid is secreted by parietal cells of the
stomach in response to stimuli such as the presence of food in the stomach or intestine and the taste, smell, sight or thought of food.
Such stimuli result in the activation of histamine, acetylcholine or gastrin receptors (the H2, M3 and CCK2 receptors, respectively) located
in the basolateral membrane of the parietal cell, which initiates signal transduction pathways that converge on the activation of the
H+/K+-ATPase, the final step of acid secretion. Inhibition of this proton pump has the advantage that it will reduce acid secretion
independent of how secretion is stimulated, in contrast to other pharmacological approaches to the regulation of acid secretion; for
example, the inhibition of acid secretion by H2 receptor antagonists can be overcome by food-induced stimulation of acid secretion
through gastrin or acetylcholine receptors.
Reprinted from Nat Rev Drug Discov 2003;2:132-9.

(the rate-limiting step). This compound forms a covalent

disulfide bond with surface-exposed cysteines of the active
parietal cell H+/K+-ATPase thus inhibiting its activity.
The five marketed PPIs, pantoprazole (Protonix, Wyeth
Pharmaceuticals, Inc., Philadelphia, PA), lansoprazole (Prevacid,
TAP Pharmaceuticals, Japan), omeprazole (Prilosec, AstraZeneca
PLC, London, England), esomeprazole (Nexium, AstraZeneca
PLC, London, England) and rabeprazole, may show subtle
difference in their ability to suppress acid owing to differences
in stability of the two-ringed structures formed by the
disulfide bond.
Rabeprazole has the highest pKa ( 5.0, the pH at
which a drug becomes 50% protonated) of the available
PPIs. Therefore, the drug can be activated at a higher pH.
In one study, at a pH of 1.2 (the pH of the parietal cell
canalicular space after a meal), rabeprazole took 1.3 min to
be half-activated in vitro, compared with 2.0, 2.8 and 4.6 min,
respectively, for lansoprazole, omeprazole and pantopazole [1].
120

At levels of fasting pH of 5.1, the activation half-life was

again substantially shorter for rabeprazole at 7.2 min, followed
by 90, 84 and 282, respectively, for the other PPIs [1]. In a
porcine model, rabeprazole demonstrated a rapid onset of
action and achieved maximal inhibition of the proton pump
within 5 min of drug exposure. Similar targets were reached
with lansoprazole and omeprazole at 30 min. Pantoprazole
proved to be the slowest with only 50% of pumps inhibited
at 50 min [2].
In 2003 Miner et al. did a randomised, open-label,
comparative, five-way crossover study that compared the
24-h intragastric pH profile of PPIs in 34 subjects [3].
Esomeprazole 40 mg, lansoprazole 30 mg, omeprazole
20 mg, pantoprazole 20 mg, and rabeprazole 20 mg were
given once daily for 5 mornings 30 min before the patients
morning meal. Day 5 intragastric pH was maintained > 4.0 for
a mean of 14.0 h with esomeprazole, 12.1 h with rabeprazole,
11.8 h with omeprazole, 11.5 h with lansoprazole and 10.1 h

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Dadabhai & Friedenberg

with pantoprazole. Although the conclusion of this study

was that esomeprazole maintained a lower intragastric pH
for a longer period, a relatively higher dose of esomeprazole
(40 mg) was used for comparison to the other PPIs. At relatively
lower doses, rabeprazole was able to effectively suppress acid
for longer than three of the other drugs in this class.
The rate of duodenal ulcer healing correlates closely with
the duration of acid suppression. Healing is best correlated
with an intragastric pH > 3 for a minimum of 18 20 h/day.
Erosive GERD healing requires an intra-oesophageal pH > 4
throughout the entire day [4,5]. In a study by Williams et al.,
rabeprazole was able to maintain prolonged acid suppression resulting in a higher median 24-h intragastric pH
compared with omeprazole [6]. The mechanism theorised by
Pantoflicka et al. was that the higher pKa of rabeprazole
maintains longer proton pump inhibition [7]. In a comparative
trial of 18 H. pylori negative adults, rabeprazole 20 mg
reached a median 24-h gastric pH of 3.4 as compared with
2.9 for lansoprazole 30 mg, 2.2 for pantoprazole 40 mg, 1.9
for omeprazole 20 mg and 1.3 for placebo. Rabeprazole
maintained a pH > 4 for 8 h versus the other PPIs, which
ranged between 3.0 and 7.4 h p < 0.04 (Figure 2) [7].
2.2

Pharmacokinetics

Rabeprazole is manufactured as an enteric coated formulation

secondary to the instability of all PPIs in the acidic gastric
environment. Following oral ingestion, it is relatively rapidly
absorbed and the peak plasma concentration reaches
2.8 5.1 mg/ml [8]. Overall bioavailability is 52% with a
standard dose of 20 mg. Rabeprazole does not have a saturable
first-pass metabolism and can be absorbed continually at
higher doses. After repeated ingestion of rabeprazole, no
significant accumulation occurs because the elimination half-life
is 1 h after single and 1.5 h after several administrations. Of
a 20 mg dose, 90% is excreted in the urine and 10% in
the faeces [8-10].
The primary metabolic pathway of rabeprazole is a
non-enzymatic conversion to rabeprazole-thioether. A minor
pathway of metabolism is via the cytochrome P450 liver
isoenzymes CYP2C19 and CYP3A4. It is notable that
CYP2C19 is the primary metabolic pathway of omeprazole,
lansoprazole, esomeprazole and pantoprazole [11]. The pharmacokinetics and pharmacodynamics of PPIs are dependent on
the genotypes of the CYP2C19. The genotypes are classified
as rapid metabolisers (RM), intermediate metabolisers (IM)
and poor metabolisers (PM). Intragastric pH and plasma
PPI levels are lowest in the RM group followed by the IM,
and then the PM group. Genetically determined differences
in the activity of this isoenzyme have been shown to influence
the cure-rates of GERD and H. pylori infection [12,13]. The
unique catabolic pathway of rabeprazole allows it to be less
susceptible to the influence of genetic polymorphisms for
CYP2C19. The predictability of rabeprazole metabolism
reduces inter-patient variability in the intragastric pH after
administration [14,15]. However, the clinical relevance of this

polymorphism has yet to be proven in long-term trials [16].

In an 8-day study by Hu et al., on 20 H. pylori-negative
Chinese volunteers, the pharmacokinetics of rabeprazole was
found to be dependent on CYP2C19 status but the end
point acid-inhibitory efficacy of rabeprazole and the gastrin
level were not significantly influenced [17].
The largely non-enzymatic metabolism of rabeprazole
partially accounts for fewer drugdrug interactions between
this PPI and other P450 isoenzyme dependent medications.
Co-administration of rabeprazole with P450 metabolically
dependent medications such as theophylline, diazepam,
warfarin and phenytoin does not interfere with their
pharmacokinetics [18]. However, rabeprazole and all other
PPIs interfere with the absorption of certain drugs that
require gastric acidity such as ketoconazole and digoxin [19].
2.3

Clinical efficacy
Gastroesophageal reflux disease

2.3.1

Gastroesophageal reflux disease is a common disease with an

increasing prevalence in Western nations. The spectrum of
GERD ranges from non-erosive reflux disease (NERD) to
severe, erosive disease. Symptoms can occur in the presence
or absence of endoscopically proven mucosal damage.
Symptoms from increased oesophageal exposure of gastric
acid include heartburn, belching, chest pain and regurgitation.
In a 2-week placebo-controlled trial, rabeprazole was both rapid
and effective in relieving heartburn on day 1 of therapy
and improved other GERD-related symptoms including
regurgitation, belching, bloating, early satiety and nausea [20].
2.4

Non-erosive reflux disease

Kahrilas reported on the rapidity of symptom relief

with 4 weeks of rabeprazole treatment in patients with
moderate-to-severe Non-erosive reflux disease (NERD) [21].
Data were combined from two similarly designed, double-blind,
placebo-controlled, multicenter US trials in which
261 patients were asked to record daily acid reflux symptoms.
Median time to 24-h heartburn-free status was significantly
reduced in the rabeprazole group (3.5 versus 19 days in
placebo) and complete heartburn relief at 4 weeks was 32%
with rabeprazole versus 3.8 with placebo (p < 0.0002).
A study by Fock et al. evaluated the efficacy of rabeprazole
compared with esomeprazole in Asian patients with
NERD in a double-blind study. The 134 participants were
divided into two groups, and randomised to treatment with
either rabeprazole 10 mg or esomeperazole 20 mg for
4 weeks. Each group kept a diary about their reflux
symptoms. Results demonstrated that both drugs were
comparable in time needed to achieve complete 24-h
heartburn-free status; 8.5 versus 9.0 days (p = NS). Rabeprazole
and esomeprazole were also statistically equivalent (p = NS)
for time to improvement in regurgitation 6.0 versus
7.5 days, respectively, global symptom improvement
(96 versus 87.9%) and satisfactory relief of nighttime symptoms
(98 versus 81.4%) [22].

Expert Opin. Drug Saf. (2009) 8(1)

121

Rabeprazole

Rabeprazole 20 mg
Lansoprazole 30 mg
Pantoprazole 40 mg
*

10

Time pH > 4 (h)

8.0

4.0

3.5

7.4

4.9
#

3.0

2.9
0.9

Omeprazole MUPS 20 mg

B.

3.4

Omeprazole 20 mg
Placebo

2.9

3.0

2.5

2.2

1.8

2.0

1.9

1.5

1.3

1.0
0.5

0
24 h

4.0
3.5

3.6

D.

3.3

3.0
#

2.5

4.0
3.5

2.2

2.1

1.8

2.0
1.5

1.3

1.0

Median gastric pH

C.
Median gastric pH

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Median gastric pH

A.

3.0
2.5
2.0
1.5

2.3

2.1
1.6

1.5

1.6
1.2

1.0
0.5

0.5

Night-time

Daytime

Figure 2. 24 h antisecretory activity of different proton-pump inhibitors in healthy volunteers. A. Time pH > 4 h; B. Median 24 h
pH. C. Median daytime pH. D. Median night-time pH.
Reprinted from Drugs 2003;63(24);2739-54 as extracted from [7].
*p 0.03 versus lansoprazole.
p 0.03 versus pantoprazole.
p 0.02 versus omeprazole.
p 0.04 versus omeprazole MUPS.
#p 0.04 versus placebo.
MUPS: Multiple unit pellet system.

2.5

Erosive oesophagitis

For erosive oesophagitis therapy, studies have aimed to identify

differences in the speed of symptom relief and mucosal healing.
A total of 85 patients with erosive reflux oesophagitis
were selected to receive omeprazole 20 mg/day, lansoprazole
30 mg/day or rabeprazole 20 mg/day for 8 weeks [23].
Daily symptoms on these therapies were assessed for
the first 7 days of administration. Whereas there was
a decrease in mean heartburn score with rabeprazole
therapy at the initial study interval of 1 week, the 8-week
comparison showed no endoscopic difference in rate of
oesophagitis healing.
Maintenance of erosive reflux healing was evaluated
by Thjodleifsson and colleagues in a 2003 study [24]. A
122

total of 243 patients who had previous response to

treatment for acute GERD were randomised to 5 years of
continuous therapy with 10 or 20 mg/day of rabeprazole
or 20 mg/day of omeprazole. The primary outcome measure
was endoscopically evident relapse of erosive oesophageal
disease. Participation to the end of the 5-year study was
achieved by 123 patients (51%), with similar completion
rates in all three groups. Of 78, 9 patients (11.5%), 8 of
82 (9.8%) and 11 of 83 (13.3%) experienced relapses in the
rabeprazole 20 mg, rabeprazole 10 mg and omeprazole
20 mg groups, respectively. All of the treatments were well
tolerated during these 5 years and no significant differences
between the study groups were seen in terms of relapse
severity or rates.

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2.5.1

On-demand treatment for episodic reflux

On-demand therapy, or therapy that is administered when

the patient experiences symptoms, has also been investigated
using rabeprazole. Rabeprazole has a favourable profile for
on-demand therapy as it achieves optimal gastric acid
suppression more rapidly than other available PPIs (5 6 h).
In one study, 55 patients were treated with rabeprazole
20 mg for a 6 month on-demand period after a run-in
period of 4 continuous weeks of therapy [25]. At the conclusion
of the study, 85% of the patients maintained symptom
control (< 2 heartburn episodes a week) with episodic,
on-demand therapy. The mean number of PPI tablets used
per day was 0.3. Patient satisfaction score at the end of the
acute 4-week trial was 98 (range: 0 100) and remained
high during the on-demand period with a median score of
90 [25]. Successful on-demand treatment has been demonstrated
with other PPIs; however, no comparative trials between
PPIs have been done for this purpose.
2.6

Atypical or extra-oesophageal reflux symptoms

Extra-oesophageal disorders thought to be related to GERD

include asthma, cough, laryngitis, ear pain/otitis and sleep
disorders. A recent Cochrane review stated that there was a
paucity of studies linking GERD to these disorders and
questioned the effect of PPI therapy in their management [26].
Most studies linking GERD to extra-oesophageal symptoms
have been open-label and uncontrolled.
Two theories link GERD and asthma. Bronchoconstriction
may be related to microaspiration of refluxed oesophageal
contents [27]. Another theory is based on the fact that the
innervation of the human bronchus and oesophagus share a
common embryologic origin. Reflux of acid into the oesophagus
elicits a vago-vagal reflex leading to acetylcholine release at
bronchial smooth muscle muscarinic receptors. This pathway
leads to cholinergic-mediated bronchoconstriction [28].
Improvement in peak expiratory flow (PEF: a measure
of the severity of obstructive airways disease) has been
evaluated in patients suffering from concomitant asthma
and GERD. Treatment with rabeprazole 20 mg/day was
found to improve PEF by > 20% in 40% of asthma patients
who were non-steroid dependent [29]. In an animal model,
Oribe showed that rabeprazole and not histamine blockers
directly decreased the hypersensitivity cough reflex induced
by an antigenic aerosol in guinea pigs and provoked with
capsaicin 24 h later [30].
Chronic laryngitis, manifested by hoarseness, throat pain
and frequent throat clearing has also been hypothesised to
be related to gastro-laryngeal reflux of acid. An open-label study
assessed the efficacy of 8 weeks of rabeprazole 20 mg b.i.d.
in patients with chronic idiopathic laryngitis without
typical GERD symptoms [31]. The study found that hoarseness,
pharyngeal pain and laryngeal signs resolved in 68.7, 78.5
and 50 80%, respectively. Weakness in the tension of the
vocal cords, which was seen in these patients before the trial
and that has been linked with chronic laryngitis, was not

improved after treatment. Also, in a post-hoc analysis by

Steward et al. these results were only consistently reproduced
in patients with aggressive lifestyle modification for reflux disease.
The addition of rabeprazole in the absence of lifestyle modification did not produce significant symptom improvement [32].
In a recent systematic review Qadeer et al. concluded
that PPI therapy may offer a modest but nonsignificant
clinical benefit over placebo in suspected GERD-related
chronic laryngitis [33].
3.

Drug safety

3.1

Kidney and liver disease

The pharmacologic profile of rabeprazole is altered in the

elderly with the Cmax (the maximal plasma concentration) of
rabeprazole being increased by 60% and the AUC (area under
the curve) doubled after 7 continuous days of treatment
with rabeprazole 20 mg. In patients with mild-to-moderate
compensated hepatic dysfunction the Cmax increased by 50%
and AUC doubled after a single dose of rabeprazole 20 mg.
Similar results were not seen in patients with renal failure.
After a single dose of rabeprazole 20 mg on the day after
haemodialysis, no difference was found in the pharmacokinetics
of the drug and no dose adjustment was required compared
to 10 healthy volunteers [34].
3.2

Reproductive safety

Reproductive studies have been performed in rats and

rabbits at intravenous dosages 13 times the recommended
human dose on the basis of the area under the plasma
concentration curve data. These studies found no evidence
that high doses of rabeprazole impaired fertility or caused
foetal harm [34]. It is not known if rabeprazole crosses
the human placenta. The molecular weight ( 381 for
the sodium salt) is low enough for the passage to the
foetus to be expected [35]. Omeprazole, another PPI, has a
similar molecular weight and chemical structure and it is
known to cross the human placenta [36]. Reports describing
the use of rabeprazole during human pregnancy have
not been done. Human pregnancy data with two other
PPIs (lansoprazole and omeprazole) has not shown a causal
relationship with congenital malformations [37,38]. However,
lack of systematic follow-up evaluations has not allowed
for proper risk assessment for exposed foetuses. As with all
drug therapy, avoidance of rabeprazole during pregnancy,
especially during the first trimester, is the safest course. If
rabeprazole is required, or if inadvertent exposure does
occur early in gestation, the known risk to the embryo/foetus
for congenital defects, on the basis of animal data for
rabeprazole and the published experience with other PPIs,
seems to be low [34].
3.3

Breast-feeding summary

Studies describing the use of rabeprazole during human

lactation have not been reported.

Expert Opin. Drug Saf. (2009) 8(1)

123

Rabeprazole

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The drug is excreted into the milk of lactating rats.

Moreover, the drug concentrated in rat milk, reaching levels
2 7 times the concentrations found in the plasma, after
administration of 14C-labelled rabeprazole. Decreased weight
gain of pups was observed when the drug was administered
to rats in late gestation and during lactation at a dose
195 times the recommended human dose based on body
surface area [39]. The clinical significance of this in humans
is unknown. This animal data suggests that rabeprazole will
likely be excreted into human milk. Therefore, the use of
rabeprazole during lactation should probably be avoided
until more clinical data are available.
4.

Adverse events

Worldwide, over 2,900 patients have been treated with

rabeprazole in Phase II III clinical trials involving various
dosages and durations of treatment. In general, rabeprazole
has been well tolerated in both short- and long-term trials.
Reported adverse event rates were similar between the
10 and 20 mg dosages. In controlled North American
and European trials, the incidence of headache was 2.4%
(n = 1,552) versus 1.6% (n = 258) for placebo [40]. This was
noted as the most common side effect followed by rash in
2.9% of patients as compared to 0 for placebo. Other rare
side effects were noted to occur in < 1 in 1,000 patients and
causality was not necessarily linked with the administration
of rabeprazole sodium.
5.

Laboratory abnormalities

The following changes in laboratory parameters have been

reported as adverse events as per the manufacturers of
rabeprazole sodium: abnormal platelets, albuminuria, increased
creatine phosphokinase, abnormal erythrocytes, hypercholesteremia, hyperglycemia, hyperlipidemia, hypokalemia,
hyponatremia, leukocytosis, abnormal liver function tests,
increased prostatic specific antigen, increased serum glutamic
pyruvic transaminase (SGPT) and urine abnormality. In
controlled clinical studies, 3 of 1,456 (0.2%) patients treated
with rabeprazole and 2 of 237 (0.8%) patients treated
with placebo developed increased (1.25 baseline value)
serum glutamic oxaloacetic transaminase (SGOT) (aspartate
aminotransferase; AST), SGPT (aspartate aminotransferase;
ALT) or both. Clinical manifestations of these abnormalities
with chills, fever, right upper quadrant pain, nausea or
jaundice were absent.
6. Combination treatment with amoxicillin
and clarithromycin for H. pylori

most commonly reported drug-related adverse events for

patients who received RAC therapy for 7 or 10 days were
diarrhoea (8 and 7%) and taste perversion (6 and 10%),
respectively [41]. The drug combinations did not produce
any clinically significant laboratory abnormalities specific to
the co-administration.
7.

Post-marketing adverse events

Few adverse events have been reported with the use of

rabeprazole based on the manufacturers data and package
inserts. These events have never been correlated directly
with the use of the drug. These events have included sudden
death; coma and hyperammonemia; jaundice; rhabdomyolysis;
disorientation and delirium; anaphylaxis; angioedema;
bullous and other drug eruptions of the skin; severe dermatologic reactions, including toxic epidermal necrolysis
(some fatal), StevensJohnson syndrome and erythema
multiforme; interstitial pneumonia; interstitial nephritis;
and thyroid-stimulating hormone (TSH) elevations. Adverse
haematologic effects including agranulocytosis, haemolytic
anaemia, leukopenia, pancytopenia and thrombocytopenia
have also been reported.
8.

Expert opinion

Proton pump inhibitors are important in the treatment

of acid-related diseases including peptic ulcer disease,
oesophagitis, non-erosive reflux disease and to a lesser extent
in GERD-related extra-oesophageal symptoms. Of the
PPIs available, data suggest that rabeprazole is at least as
effective as the others and may confer an advantage by using
a non-enzymatic metabolic pathway. For patients having
genetic polymorphisms of CYP2C19 who metabolise PPIs
faster and for those patients who take other medications
dependent on the P450 metabolism, rabeprazole may be the
safest PPI. The theoretical advantages of rabeprazole are
primarily based on its higher effective pKa. This leads to
faster drug activation and a longer duration of action than
others in its class. However, in head-to-head clinical
comparisons of PPI medications, trials have not demonstrated a statistically significant advantage for rabeprazole.
On-demand therapy for rabeprazole may be important
for this drug in the future as rabeprazole achieves maximal
H+/K+-ATPase inhibition faster than the other PPIs. The
role of maintenance therapy for this drug after achievement
of endoscopically healed GERD or non-erosive reflux disease
could be explored, although data suggest that the efficacy of
rabeprazole would be similar to other PPIs in this capacity.

Declaration of interest
In co-administration clinical trials with rabeprazole plus
amoxicillin and clarithromycin (RAC) for H. pylori eradication,
no adverse events specifically related to these medications
were observed. In a multicenter trial of 803 patients, the
124

No financial support was received. FK Friedenberg has

previously received research funding from Eisai Co. Ltd and
AstraZeneca PLC.

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Affiliation
Alia Dadabhai MD &
Frank K Friedenberg MD MS
Author for correspondence
Temple University Hospital,
Temple University School of Medicine,
Gastroenterology Section,
Parkinson Pavilion, 8th Floor,
3401 North Broad Street,
PA 19140, Philadelphia, USA
Tel: +1 215 707 3431; Fax: +1 215 707 2684;
E-mail: friedfk@tuhs.temple.edu