Oral esomeprazole vs. intravenous pantoprazole: a comparisonof the effect on intragastric pH in healthy subjects

D. ARMSTRONG*, D. BAIR*, C. JAMES*, L. TANSER� , S. ESCOBEDO� & K. NEVIN�*Division of Gastroenterology, McMaster University & Hamilton Health Sciences, Hamilton, ON, Canada; and �AstraZeneca

Canada Inc., Mississauga, ON, Canada

Accepted for publication 10 July 2003

SUMMARY

Background: Intravenous (IV) proton-pump inhibitor

therapy is used in patients who cannot take oral

medications or require greater acid suppression. Oral

esomeprazole produces greater acid suppression than

oral pantoprazole; however, no comparative data exist

for oral esomeprazole and IV pantoprazole.

Aim: To compare acid suppression (time with pH > 3.0,

4.0, 5.0 and 6.0) produced by standard doses of oral

esomeprazole and IV pantoprazole in healthy subjects.

Methods: A randomized, two-way crossover study in

30 subjects receiving oral esomeprazole (40 mg o.d.)

or IV pantoprazole (40 mg o.d.) for 5 days followed by

a 2-week washout period before the second 5-day drug

administration period using the crossover drug

regimen.

Results: Oral esomeprazole produced greater acid sup-

pression than IV pantoprazole on day 1 [pH > 3.0

(56.9%, 35.8%; P < 0.001), pH > 4.0 (43.4%, 25.0%;

P < 0.001) and pH > 5.0 (28.7%, 15.6%; P < 0.001)]

and on day 5 [pH > 3.0 (70.4%, 45.9%; P < 0.001),

pH > 4.0 (59.2%, 33.9%; P < 0.001), pH > 5.0

(45.5%, 23.9%; P < 0.001) and pH > 6.0 (19.6%,

12.6%; P ¼ 0.045)]. The adverse event profiles indica-

ted both treatments to be safe and well tolerated.

Conclusions: In healthy subjects, esomeprazole, 40 mg

o.d. dispersed in water, produces greater acid suppres-

sion than pantoprazole 40 mg IV o.d. after 1 and 5 days

of medication.

INTRODUCTION

Oral proton-pump inhibitor therapy produces a high

degree of acid suppression and is very effective for the

management of acid-related disorders. High-dose, intra-

venous proton-pump inhibitor therapy given as a bolus

followed by a continuous infusion is recommended for

patients with upper gastrointestinal haemorrhage;

intravenous proton-pump inhibitor therapy may also

be required for patients who are unable to take oral

medication.1, 2 Currently, pantoprazole is the only IV

proton-pump inhibitor commercially available in North

America, and its use in the hospital environment has led

to increasing concerns about appropriate use of IV acid

suppressants and the potential for increased costs.3, 4

With this in mind, oral proton-pump inhibitors might be

prescribed more readily for hospital inpatients if it could

be shown clearly that they are comparable to IV proton-

pump inhibitors.

Esomeprazole, the S-isomer of omeprazole, has an

improved pharmacokinetic profile leading to greater

acid suppression than that produced by omeprazole,

pantoprazole, lansoprazole and rabeprazole.5 In clinical

studies, the greater acid suppression produced by

esomeprazole has translated into higher healing rates

and more effective symptom relief when compared to

lansoprazole and omeprazole in gastro-oesophageal

Correspondence to: Dr D. Armstrong, Division of Gastroenterology, HSC-

4W8, McMaster University Medical Centre, 1200 Main Street West,

Hamilton, Ontario L8N 3Z5, Canada.

E-mail: armstro@mcmaster.ca

Aliment Pharmacol Ther 2003; 18: 705–711. doi: 10.1046/j.1365-2036.2003.01743.x

� 2003 Blackwell Publishing Ltd 705

reflux disease (GERD) patients.6–8 A recent study

showed no difference between the oral and IV formu-

lations of pantoprazole (20 and 40 mg) with respect to

reduction of gastric acid output in patients with GERD.9

Furthermore, subjects who received 30 mg of lansop-

razole (administered nasogastrically with apple sauce)

demonstrated a higher 24-h intragastric pH and

sustained more intragastric pH than when they received

40 mg of pantoprazole IV.10 Thus, it can be postulated

that oral esomeprazole will produce acid suppression

greater than that produced by IV pantoprazole.

Oral esomeprazole, which is available in many coun-

tries as a dispersible, multiple-unit, enteric-coated pellet

formulation, can be used in patients with a nasogastric

tube in situ. Stability data for the multiple unit pellet

system (MUPS) tablet has shown the enteric-coated

pellets to remain intact for up to 30 min when dispersed

in water or in apple sauce and to be bioequivalent to the

intact tablet.11, 12 The purpose of this study was to

compare the pharmacodynamics, and thereby the

degree of acid suppression, produced by standard doses

of oral esomeprazole and IV pantoprazole by comparing

the median 24-h pH values and the percentages of the

24-h recording period during which intragastric pH was

greater than 3, 4, 5 and 6 on days 1 and 5 of drug

administration in healthy Helicobacter pylori negative

subjects. The primary hypothesis of this study was that

oral esomeprazole administered as an oral suspension

produces greater acid suppression than IV pantoprazole,

as indicated by the time during which intragastric pH is

greater than 4.0 on day 1 of drug administration.

MATERIALS AND METHODS

Subjects

Thirty healthy male and female subjects participated in

a single-centre study at the McMaster University

Medical Centre site of Hamilton Health Sciences.

Subjects were enrolled if a prescreen assessment

indicated a normal medical history, physical examina-

tion, electrocardiogram (ECG) and laboratory findings.

Inclusion in the trial required written informed

consent from the subject, a body mass index (BMI)

between 19 and 27 kg/m2 and weight between 50 and

100 kg. Absence of H. pylori infection was established

by 13C-urea breath test (UBT) (Isodiagnostika Inc.,

Edmonton, AB, Canada); breath samples were analysed

at McMaster University Medical Centre by isotope ratio

mass spectrometry according to standard protocols

(Breath Mat, Finnigan Mat, Bremen, Germany). The

major exclusion criteria were the presence of any

upper gastrointestinal tract symptoms, any significant

concurrent disease or clinical illness during 14 days

prior to enrolment, a blood donation or the use of an

investigational drug or device within 12 weeks prior to

enrolment, the use of prescription drugs within

14 days prior to baseline pH recording, or the use of

over-the-counter drugs within 7 days prior to the

baseline visit; acetaminophen and oral contraceptives

were permitted. Proton-pump inhibitors, prokinetic

agents, antibiotics and bismuth-containing compounds

were not allowed for 30 days prior to baseline

recordings. Subjects with a history of past or current

drug or alcohol abuse were ineligible, as were female

subjects who were pregnant or lactating.

Design

This was a randomized, open-label, two-way crossover

study. After an initial prescreen visit to determine

eligibility and a 24-h baseline pH recording within

2 weeks of drug administration, subjects were random-

ized to initial therapy with either oral esomeprazole

(40 mg o.d.), administered as an oral suspension or

IV pantoprazole (40 mg o.d.) for five consecutive days.

This was followed by a 2-week washout period before

the second 5-day drug administration period using the

crossover drug regimen. Subjects were instructed not to

smoke or use alcohol at any time during the trial

(Figure 1).

Oesophageal manometry was performed during the

prescreen visit to determine the location of the lower

oesophageal sphincter (LOS). The pH electrode was

passed transnasally into the stomach and positioned

10 cm below the manometrically defined LOS. Sequen-

tial gastric pH values were recorded every 4 s by the

data recorder, and then downloaded to a native format

Esomeprazole(oral 40 mg od)

Pantoprazole(IV 40 mg od)

Day 1 5 Day 1 5

pH pH

Washout Period> 14 days

Esomeprazole(oral 40 mg od)

Pantoprazole(IV 40 mg od)

pHpHpHBaseline

Pre-screen

Observation> 7 days

Figure 1. Study flow chart.

706 D. ARMSTRONG et al.

� 2003 Blackwell Publishing Ltd, Aliment Pharmacol Ther 18, 705–711

Medtronic pH data file before conversion to an ASCII file

for analysis. Analysis of pH data was performed

according to established techniques using dedicated

software for summary and graphical presentation.13 In

all, five ambulatory pH recordings were performed using

a single-channel, internally referenced glass pH elec-

trode (Ingold M440, Medtronic) attached to a Digitrap-

per III pH data recorder (Medtronic, Mississauga, ON,

Canada); one 24-h recording was performed on days 1

and 5 of drug administration after an initial, baseline

pre-treatment recording.

Subjects fasted from midnight until the start of the

recording the following morning, and were then

provided with one of two standard nutrition regimens

based on body weight. Each regimen consisted of three

meals and one snack for each day of pH recording.

Breakfast was taken 1 h following pH probe place-

ment, lunch was taken between 12:00 and 13:00,

dinner between 18:00 and 19:00 and a light snack at

20:00. Routine clinical chemistry and haematology

were performed at the prescreen visit and on day 5 of

drug administration for evaluation of safety data (Core

Laboratory, Hamilton Health Sciences, Hamilton, ON,

Canada). A serum human chorionic gonadotropin

(hCG) test was performed for all female subjects at

the prescreen visit, day 1 of the second drug admin-

istration period and on the final visit. A follow-up

telephone contact was arranged 2 weeks following the

last visit (the fifth day of drug administration during

the second crossover treatment period) to monitor

subjects for ongoing adverse events.

Study drug

Esomeprazole MUPS tablets (rapid dispersible formula-

tion; AstraZeneca R & D, Molndal, Sweden) 40 mg,

were taken orally once each morning on the days of

drug administration. Tablets were dispersed in 100 mL

of noncarbonated, room-temperature water and stirred

for approximately 2 min, until the tablet had dispersed

completely; stability data indicate that the enteric-

coated pellets of esomeprazole remain intact for up to

30 min after dispersal in water.11 The solution was

drunk within 15 min of dispersal and the glass was

rinsed with 100 mL of water, which was drunk

immediately to ensure ingestion of any tablet residue.

Pantoprazole IV solutions were also administered once

daily in the morning. The solution was prepared by

injecting 10 mL of 0.9% NaCl into the vial containing

the dry lyophilized powder (pantoprazole 40 mg; pan-

toprazole sodium 42.3 mg; Altana Pharma, Constanz,

Germany). The reconstituted solution, diluted with

90 mL of 0.9% NaCl injection, was infused over

15 min and used within 6 h of preparation.

Statistics

The number of subjects was calculated to demonstrate

that oral esomeprazole (40 mg o.d.) is more effective in

controlling intragastric pH, to IV pantoprazole (40 mg

o.d.) by at least 6% with respect to the percentage of

time during which pH was greater than 4.0 on day 1.

Assuming a within-subject standard deviation of 11%,

detection of a difference of this magnitude, with a power

of 0.8 and a type I error of 0.05, required 26 subjects.

Assuming a dropout rate of 20% (including protocol

violators, technical failures and withdrawals), 30 vol-

unteers were included.

For each 24-h recording period the median 24-h pH

was calculated. Statistical analysis used parametric

tests and presented the data as the mean of the median

24-h pH values. A mixed analysis of variance (anova)

was carried out for the percentage of time that gastric

pH was greater than 3.0, 4.0, 5.0 and 6.0, with the

mean of the 24-h median pH as the dependent

variable, the sequence, period and treatment as fixed

effect factors, and the subject as a random effect factor.

Confidence intervals and P-values were used to assess

the treatment effects within and between treatments.

Ninety-five percent confidence interval estimates of the

individual true mean effects, least-square means (LSM)

of percentage time pH > 3.0, 4.0, 5.0 and 6.0 were

calculated. The percentages of subjects having a pH

greater than 3.0, 4.0, 5.0 and 6.0 for the first 4 h of

each recording were also calculated and compared

between treatments for day 1 using the v2-test.

Likewise, the number of subjects that maintained their

pH greater than 4.0 during 12 and 16 h after drug

administration during both days 1 and 5 were

compared between esomeprazole and pantoprazole

using McNemar’s test. A spline interpolation was used

to smooth the individual pH data for the 24-h pH data

plot.

RESULTS

Thirty subjects were randomized and received at least

one dose of study medication. Two subjects were

GASTRIC pH WITH ORAL ESOMEPRAZOLE OR IV PANTOPRAZOLE 707

� 2003 Blackwell Publishing Ltd, Aliment Pharmacol Ther 18, 705–711

excluded from selected analyses due to technical failures

leading to the loss of pH and other data; one subject had

incomplete pH data and the other had incomplete

demographic data, pK data and pH data due to technical

failure. Demographics for the 29 subjects with complete

pH data (20 males; 9 females) showed a mean (s.d.) age

of 25.3 (5.9) years, weight 77.5 (10.5) kg, height

175.4 (9.3) cm and BMI 25.1 (1.9) kg/m2.

Oral esomeprazole produced a significantly greater

percentage of time during which pH was greater than

4.0 compared to pantoprazole IV on day 1 of drug

administration (43.4, 25.0; P < 0.001). Similarly, on

day 1 of drug administration, oral esomeprazole

produced a significantly greater percentage of time with

pH greater than 3.0 (56.9, 35.8) and 5.0 (28.7, 15.6)

(P < 0.001) compared with IV pantoprazole. There

were no significant differences between the two

treatments with respect to the percentage of time with

pH > 6.0 on day 1 (10.5, 7.5; P ¼ 0.27). Similar

results were observed on day 5; oral esomeprazole

produced a significantly greater percentage of time with

pH greater than 3.0 (70.4, 45.9), 4.0 (59.2, 33.9), 5.0

(45.5, 23.9) (P < 0.001 for all) and 6.0 (19.6, 12.6;

P ¼ 0.045) compared with IV pantoprazole (Figure 2).

Oral esomeprazole produced a greater increase in

intragastric pH on day 1 that was evident throughout

the 24-h recording periods, compared with IV pantop-

razole (Figure 3). At baseline the group mean value

% 2

4-hr

rec

ordi

ng

0

10

20

30

40

50

60

70

80

90

100

pH > 4.0 pH > 5.0 pH > 6.0pH > 3.0

pH threshold

* P < 0.05

** P < 0.001

****

**

**

**

**

*

Esomeprazole day 1Pantoprazole day 1Esomeprazole day 5Pantoprazole day 5

Figure 2. Mean percentages of the 24-h

recording period (95% CI) on day 1 (first 2

bars) and day 5 (last 2 bars) during which

intragastric pH exceeded thresholds of 3.0,

4.0, 5.0 and 6.0 for esomeprazole (dark

bars) and pantoprazole (light bars).

Med

ian

pH

B L D Sn

Day 1

Figure 3. Median 24-h intragastric pH

curves (n ¼ 28) for day 1 showing the

baseline pH curve (before therapy) as a

reference for each graph (solid line,

esomeprazole; dashed line, pantoprazole).

Arrows indicate the timing of the standard

meals (B, breakfast; L, lunch; D, dinner;

Sn, snack).

708 D. ARMSTRONG et al.

� 2003 Blackwell Publishing Ltd, Aliment Pharmacol Ther 18, 705–711

[95% confidence interval (CI)] for the median 24-h pH

was 1.75 (1.63–1.87), and on day 1 oral esomeprazole

[mean 3.6 (3.2–4.0)] produced a higher median 24-h

pH than IV pantoprazole [2.5 (2.1–2.9); P < 0.001].

This difference was maintained (Figure 4) at day 5 [oral

esomeprazole: 4.6 (4.2–5.0) compared with IV panto-

prazole: 2.9 (2.5–3.3); P < 0.001].

Intragastric pH was greater than 4.0 for 12 or more

hours in 35.7% and 3.6% of esomeprazole and pantop-

razole subjects, respectively, on day 1 (P ¼ 0.002) and

85.7% and 7.1%, respectively, on day 5 (P < 0.0001).

Esomeprazole maintained gastric pH > 4.0 for greater

than 16 h in 7.1% of patients compared with 3.6% for

pantoprazole on day 1 (P > 0.05), and in 32.1% of

patients compared with 3.6% pantoprazole on day 5

(P ¼ 0.005) (Figure 5).

Intragastric pH during the first 4 h of the recording on

day 1 was greater than 5.0 (esomeprazole, 96.4%;

pantoprazole, 64.3%; P < 0.01) and 6.0 (esomeprazole,

60.7%; pantoprazole, 25%; P < 0.05) in a greater

proportion of subjects after oral esomeprazole than after

IV pantoprazole; a similar trend was seen for pH greater

than 3.0 (esomeprazole, 100%; pantoprazole, 96.4%;

P > 0.05) and 4.0 (esomeprazole, 96.4%; pantoprazole,

85.7%; P > 0.05) (Figure 6). Analysis of pharmaco-

kinetic data indicates that both study drugs achieved

adequate drug levels indicative of subject compliance

with the administration schedules.

There were no significant differences in the incidence

of adverse events between the two treatments. The most

commonly reported adverse events for both treatments

were headache, sore throat, bloating and diarrhoea.

Both drugs were safe and well tolerated in all subjects.

DISCUSSION

The results of the present study are consistent with the

results of previous comparative studies. As oral

esomeprazole (40 mg o.d.) produces a greater reduc-

tion in gastric acidity than oral pantoprazole (40 mg

o.d.),14 it had been hypothesized that oral esomepraz-

ole (40 mg o.d.) would produce a greater increase in

Med

ian

pH

B L D Sn

Day 5

Figure 4. Median 24-h intragastric pH

curves (n ¼ 28) for day 5 showing the

baseline pH curve (before therapy) as a

reference for each graph (solid line, eso-

meprazole; dashed line, pantoprazole). Ar-

rows indicate the timing of the standard

meals (B, breakfast; L, lunch; D, dinner; Sn,

snack).

Esomeprazole

Pantoprazole

Day 1 Day 5

12 hours 16 hours12 hours 16 hours

35.7% 7.1% 85.7% 32.1%

3.6% 3.6% 7.1% 3.6%

Figure 5. Percentage of subjects who had

an intragastric pH greater than 4.0 for 12

and 16 h (or more) per day during

treatment on days 1 and 5 with esomep-

razole and pantoprazole.

GASTRIC pH WITH ORAL ESOMEPRAZOLE OR IV PANTOPRAZOLE 709

� 2003 Blackwell Publishing Ltd, Aliment Pharmacol Ther 18, 705–711

gastric pH than intravenous pantoprazole (40 mg

o.d.). This hypothesis was confirmed unequivocally,

and although the degree of acid suppression produced

by both proton-pump inhibitors increased from day 1 to

day 5 of administration, the difference between the

two proton-pump inhibitors was, if anything, greater

at day 5. Furthermore, oral esomeprazole produced a

greater increase in pH during the first 4 h after drug

administration on day 1, indicating that IV adminis-

tration does not necessarily produce a faster onset of

action.

For patients with acid-related disorders such as erosive

oesophagitis and peptic ulcer disease, lesion healing and

symptom relief are related directly to the degree of acid

suppression achieved by medical therapy.15–18 Proton-

pump inhibitors are the most effective acid-suppressing

agents currently available and, in the vast majority of

patients, oral proton-pump inhibitors are highly effect-

ive therapeutic agents for most acid-related disorders.

Indeed, the indications for intravenous or enteral

proton-pump inhibitor administration are quite limited;

patients requiring proton-pump inhibitors who cannot

take anything by mouth should receive their medication

intravenously. However, it is not uncommon for IV

proton-pump inhibitors to be used for patients who are

unable to swallow, even if there is a nasogastric tube

in situ. This may be due, in part, to a perception that an

oral proton-pump inhibitor is less effective than an

intravenous formulation and, in part, to concerns that

oral proton-pump inhibitors cannot be administered

easily via a nasogastric tube.

Oral esomeprazole, the S-isomer of omeprazole, has

higher bioavailability than either the R-isomer or

racemic omeprazole, and it produces a greater degree

of acid suppression at a standard, once-daily dose, with

a higher median 24-h pH, and a greater proportion of

the 24-h recording period during which gastric pH

exceeds 4.0.19 More recently, it has been reported that

oral and intravenous pantoprazole are also equivalent,

even when administered at a high dose (280–290 mg

daily) in healthy volunteers, comparable to doses used

for the management of upper gastrointestinal tract

haemorrhage (80 mg bolus, followed by an infusion of

8 mg/ h).19, 20

This study was conducted in healthy subjects, and the

results should therefore be extrapolated with caution to

patients in an intensive care unit (ICU) and those who

are being treated for upper gastrointestinal bleeding.

The baseline pH data indicate that all subjects had

normal gastric secretory function, unlike some ICU

patients in whom gastric acid secretion may be

compromised by severe concomitant illness. The route

of administration is also important, particularly for ICU

patients. Patients being treated for upper gastrointesti-

nal haemorrhage may be able to take oral medication,

but many ICU patients can take medications only

intravenously or via a nasogastric tube. In the present

study, esomeprazole was not administered nasogastri-

cally; however, given that the total volume of the

suspension is only slightly larger than that which can

be given nasogastrically, and given that the dispersed

MUPS tablet is bioequivalent to the intact tablet, it is

unlikely that the administration of an oral suspension

altered the observed intragastric pH significantly.8

Subjects in this study were not fasted, and the effect of

food ingestion on gastric pH is evident in the mean pH

curves, with pH rises occurring at 3, 6 and 12 h after

the start of the recordings (Figures 3 and 4). However,

subjects took the same standardized meals throughout

all recording periods, so the observed difference between

the two medications is very unlikely to have been meal-

related. Although the present study was conducted in

healthy subjects, there is no indication from previous

studies that differences between proton-pump inhibitors

are limited to a specific subset of individuals. The effect

of oral esomeprazole, compared with intravenous

proton-pump inhibitors, should now be tested in ICU

patients able to take proton-pump inhibitors by mouth

or nasogastric tube. In addition, these data may also

provide a basis for an appropriate transition from

intravenous to oral proton-pump inhibitor therapy for

hospital inpatients; this has important cost implications

because there are now increasing data to indicate that

pH>3.0 pH>4.0 pH>5.0 pH>6.0

Per

cent

age

of S

ubje

cts

0102030405060708090

100

Esomeprazole

Pantoprazole

pH threshold

N.S. N.S.P < 0.01

P < 0.05

Figure 6. Mean percentages of the initial 4-h segment of the

recording period (95% CI) on day 1 during which intragastric pH

exceeded thresholds of 3.0, 4.0, 5.0 and 6.0 for esomeprazole

(white columns) and pantoprazole (grey columns).

710 D. ARMSTRONG et al.

� 2003 Blackwell Publishing Ltd, Aliment Pharmacol Ther 18, 705–711

much of the current inappropriate use of intravenous

proton-pump inhibitors is due to a delayed transition to

oral medication rather because of an inappropriate

institution of intravenous therapy.3, 4, 21 The results of

this study demonstrated that oral esomeprazole dis-

persed in water produced greater intragastric acid

suppression than IV pantoprazole in equal doses

(40 mg o.d.). It is also possible, at higher doses than

those used in the current study, that oral therapy with

esomeprazole may produce greater acid suppression, at

equivalent doses, than IV pantoprazole.

ACKNOWLEDGEMENTS

Supported by an unrestricted grant from AstraZeneca

Canada Inc, Mississauga, ON, Canada.

REFERENCES

1 Lau JY, Sung JJ, Lee KK, et al. Effect of intravenous omeprazole

on recurrent bleeding after endoscopic treatment of bleeding

peptic ulcers. N Engl J Med 2000; 343: 310–6.

2 British Society of Gastroenterology Endoscopy Committee.

Non-variceal gastrointestinal haemorrhage: guidelines. Gut

2002; 51(suppl 4): iv 1–6.

3 Bair FD, Armstrong D, Zhou P. Intravenous acid suppression –

appropriateness of use in a tertiary care setting. Gastroenter-

ology 2001; 120: A730 (Abstract).

4 Zadieh I, Andrews C, Brodie M, et al. Prescribing practices and

indications for the use of intravenous proton pump inhibitors

(IV PPI) in an urban tertiary care centre. Can J Gastroenterol

2002; 16: 153.

5 Spencer CM, Faulds D. Esomeprazole. Drugs 2000; 60: 321–9.

6 Kahrilas PJ, Falk GW, Johnson DA, et al. Esomeprazole

improves healing and symptom resolution as compared with

omeprazole in reflux esophagitis patients: a randomized con-

trolled trial. Aliment Pharmacol Ther 2000; 14: 1249–58.

7 Castell DO, Kahrilas PJ, Richter JE, et al. Esomeprazole (40 mg)

compared with lansoprazole (30 mg) in the treatment of

erosive esophagitis. Am J Gastroenterol 2002; 97: 575–83.

8 Richter JE, Kahrilas PJ, Johanson J, et al. Efficacy and safety of

esomeprazole compared with omeprazole in GERD patients

with erosive esophagitis: a randomized controlled trial. Am J

Gastroenterol 2001; 96: 656–65.

9 Metz DC, Pratha V, Martin P, et al. Oral and intravenous

dosage forms of pantoprazole are equivalent in their ability to

suppress gastric acid secretion in patients with gastr-

oesophageal reflux disease. Am J Gastroenterol 2000; 95:

626–33.

10 Freston J, Chiu Y, Pan W, et al. Effects on 24-hour intragastric

pH: a comparison of lansoprazole administered nasogastrically

in apple juice and pantoprazole administered intravenously.

Am J Gastroenterol 2001; 96: 2058–65.

11 Rohss K, Hassan-Alin M, et al. Bioequivalence of esomeprazole

40mg tablet dispersed in water and the intact tablet in male

and female healthy volunteers. Gut 2002; S2: A168

(Abstract).

12 Andersson T, Magner D, et al. Esomeprazole 40 mg capsules

are bioequivalent when administered intact or as the con-

tents mixed with applesauce. Clin Drug Invest 2001; 21:

67–71.

13 Armstrong D, Emde D, et al. Long-term ambulatory gastric

pH-metry: easy to do but difficult to analyze. Eur J Gastroenter

Hepatol 1991; 1: 167–74.

14 Wilder-Smith C, Rohss K, Rydholm H, et al. Esomeprazole 40

mg provides more effective acid control than pantoprazole 40

mg. Gastroenterology 2000; 118: A20 (Abstract).

15 Jones DB, Howden CW, Burget DW, et al. Acid suppression in

duodenal ulcer: a meta-analysis to define optimal dosing with

antisecretory drugs. Gut 1987; 28: 1120–7.

16 Howden CW, Hunt RH. The relationship between suppression

of acidity and gastric ulcer healing rates. Aliment Pharmacol

Ther 1990; 4: 1990.

17 Burget DW, Chiverton SG, Hunt RH. Is there an optimal

degree of acid suppression for healing of duodenal ulcers?

Gastroenterology 1990; 99: 345–51.

18 Bell NJ, Burget D, Howden CW, et al. Appropriate acid sup-

pression for the management of gastroesophageal reflux dis-

ease. Digestion 1992; 51: 59–67.

19 Lind T, Rydberg L, Kyleback A, et al. Esomeprazole provides

improved acid control vs. omeprazole in patients with symp-

toms of gastroesophageal reflux disease. Aliment Pharmacol

Ther 2000; 14: 861–7.

20 Bair FD, James C, Armstrong D. Maximal acid suppression:

oral vs. intravenous pantoprazole. Gastroenterology 2002;

122: A476–7.

21 Kaplan GG, Bates D, McDonald D, et al. Inappropriate use of

intravenous proton pump inhibitors: Problem extent and cost

implications. Am J Gastroenterol 2002; 97: S236.

GASTRIC pH WITH ORAL ESOMEPRAZOLE OR IV PANTOPRAZOLE 711

� 2003 Blackwell Publishing Ltd, Aliment Pharmacol Ther 18, 705–711