Aliment Pharmacol Ther 2000; 14: 887±892.
Oral pharmacokinetics of omeprazole and lansoprazole
after single and repeated doses as intact capsules
or as suspensions in sodium bicarbonate
V. K. SHARMA *, B. PEY TON*, T. SPEARS*, J.-P. RAU FMAN * & C. W. HOW DEN
*Division of Gastroenterology, University of Arkansas for Medical Sciences, Little Rock, AR, USA; and  Division
of Gastroenterology and Hepatology, Northwestern University, Chicago, IL, USA
Accepted for publication 13 March 2000
SUMMARY
Background: Omeprazole and lansoprazole can be given
in sodium bicarbonate as, respectively, simpli®ed omep-
razole suspension and simpli®ed lansoprazole suspen-
sion. We previously found the antisecretory effect of
omeprazole 20 mg given as simpli®ed omeprazole
suspension to be lower than with intact capsules.
However, lansoprazole 30 mg as simpli®ed lansoprazole
suspension produced an effect similar to that seen
with intact capsules.
Aim: To evaluate the absorption of both drugs when
given orally as capsules or as suspensions in sodium
bicarbonate.
Methods: In random order, we gave 5-day courses of
omeprazole 20 mg and lansoprazole 30 mg as capsules
and as suspensions in sodium bicarbonate to 12
healthy women. Serial blood samples were taken on
INTRODUCTION
The proton pump inhibitors omeprazole and lansopra-
zole are generally administered orally as capsules of
enteric-coated granules. However, patients with swal-
lowing disorders and those with indwelling gastrostomy
or nasogastric feeding tubes may be unable to take these
Correspondence to: Dr C. W. Howden, Northwestern University,
Northwestern Center for Clinical Research, 680 N. Lakeshore Drive,
Suite 1220, Chicago, IL 60611, USA.
E-mail: c-howden@nwu.edu
Ó 2000 Blackwell Science Ltd
 
days 1 and 5 of each course for pharmacokinetic
measurements.
Results: There was impairment of omeprazole absorp-
tion when given as simpli®ed omeprazole suspension.
Maximum plasma concentration and area under the
concentration/time curve were lower with simpli®ed
omeprazole suspension than with omeprazole capsules
(P ˆ 0.034 and 0.013, respectively, on day 5). No
differences were found in lansoprazole absorption when
simpli®ed lansoprazole suspension was compared with
its standard capsule formulation. Relative bioavailability
of omeprazole from simpli®ed omeprazole suspension
compared to the capsule was 58.4% on day 5. The
corresponding value for lansoprazole was 84.7%.
Conclusions: Simpli®ed omeprazole suspension 20 mg
does not supply adequate omeprazole for systemic
absorption. Lansoprazole absorption from simpli®ed
lansoprazole suspension is maintained.
proton pump inhibitor formulations by mouth. We have
previously shown that both omeprazole and lansopraz-
ole are effective in suppressing intragastric acidity when
administered through a gastrostomy tube as intact,
non-encapsulated granules in orange juice.1, 2 Degrees
of suppression of acidity were comparable to those
reported by others for the intact capsule formulations of
omeprazole and lansoprazole.3, 4 However, there may
be a reluctance to administer intact granules of a proton
pump inhibitor through a feeding tube because of
perceived dif®culties with aggregation of granules and
tube blockage. Although we did not encounter these
887
888 V. K. SHARMA et al.
problems in our studies, we subsequently evaluated the
effectiveness of omeprazole and lansoprazole as suspen-
sions in 8.4% sodium bicarbonate.1, 2 These were
termed, respectively, simpli®ed omeprazole suspension
and simpli®ed lansoprazole suspension. The per-gas-
trostomy administration of simpli®ed lansoprazole sus-
pension raised intragastric pH to levels that were
comparable to those seen with the intact capsule
formulation of lansoprazole.5 However, simpli®ed omep-
razole suspension administered through a gastrostomy
had an effect on intragastric pH that was quantitatively
smaller than that observed with either intact omepraz-
ole capsules or intact, non-encapsulated omeprazole
granules in orange juice.6
Little is known about the absorption of either omep-
razole or lansoprazole when administered as a suspen-
sion in sodium bicarbonate. In one study, an oral
suspension of lansoprazole granules in a ¯avouring
solution produced comparable plasma levels to those
seen with the administration of intact lansoprazole
capsules.7 The administration of intact lansoprazole
granules orally in apple sauce, or via a nasogastric tube
in apple juice, produces plasma lansoprazole levels that
are comparable to those seen with the intact capsule.8, 9
The absorption of omeprazole from its standard capsule
formulation displays marked inter- and intra-individual
variability.10 Furthermore, the proportion of the omep-
razole dose that is absorbed increases with repeated
once daily administration to reach a plateau by the 5th
day.10±12 However, the bioavailability of lansoprazole
does not progressively increase with repeated daily
dosing, being near maximal after a single dose.13, 14
We conducted this study to compare the absorption
characteristics of each proton pump inhibitor when
administered after single and repeated once-daily dos-
ing, as intact capsules and as suspensions in sodium
bicarbonate.
MATERIALS AND METHODS
Twelve healthy women were recruited for the study.
Their mean (‹ s.d.) age was 36.8 (‹ 9.8) years, their
mean (‹ s.d.) weight was 73.6 (‹ 12.7) kg and their
mean (‹ s.d.) height was 1.66 (‹ 0.07) m. None had
any signi®cant past medical history of note and none
was taking any regular prescribed medication. None
had received either omeprazole or lansoprazole in the
preceding month. Each subject gave her written,
informed consent to the study, which was approved
by the institutional review board of the University of
Arkansas for Medical Sciences, Little Rock, AR.
All studies were performed in the Division of Gastro-
enterology, University of Arkansas for Medical Sciences,
Little Rock, AR. In a pre-determined random order,
subjects received each of four proton pump inhibitor
formulations once daily for 5 days. The dosing periods
were separated by 9-day washout periods. The four
formulations studied were intact omeprazole capsules
20 mg, simpli®ed omeprazole suspension 20 mg, intact
lansoprazole capsules 30 mg and simpli®ed lansoprazole
suspension 30 mg. These were taken at 08.00 hours on
each day, 30 min before the ®rst food of the day and
after an overnight fast. Study drugs were administered
in this way to mimic, as far as was reasonably possible,
the manner in which proton pump inhibitors are
usually prescribed.
On the ®rst and ®fth days of dosing, subjects had serial
blood sampling for plasma drug levels. An intravenous
cannula was inserted into an arm vein and 10 mL blood
samples were withdrawn at 0, 0.5, 1, 1.5, 2, 2.5, 3 and
6 h after dosing for, as appropriate, plasma omeprazole
or lansoprazole levels. Subjects were observed during
these times in a specialized clinical investigation unit.
Subjects had a standard breakfast 30 min after dosing
and had nothing further by mouth until the conclusion
of the study. Blood samples were collected into tubes
containing heparin sodium and centrifuged at
2500 r.p.m. for 15 min. Plasma was decanted and
samples stored at )20 °C until being shipped in batch at
the conclusion of the study to Harris Laboratories
(Lincoln, NE) for analysis.
Lansoprazole (internal standardÐomeprazole) and
omeprazole (internal standardÐlansoprazole) were
extracted from heparinized plasma into ethyl ether:
methylene chloride, 70:30 (v:v). The extracts were dried
under nitrogen and reconstituted in acetonitrile and
injected into an on-line LC/MS/MS system. Detection of
the analytes was performed with an Inertsil silica
column and a Perkin-Elmer API 365 tandem mass
spectrometer using a turbo ion spray interface. Positive
ions (m/z of 370.2±> 251.9 for lansoprazole and
346.2±> 198.1 for omeprazole) were monitored in the
MRM mode.
We have previously described the methods for the
preparation of simpli®ed omeprazole suspension and
simpli®ed lansoprazole suspension.5, 6 Brie¯y, these
were prepared by opening a 20-mg omeprazole capsule
or a 30-mg lansoprazole capsule, pouring the granular
Ó 2000 Blackwell Science Ltd, Aliment Pharmacol Ther 14, 887±892

contents into 10 mL of 8.4% sodium bicarbonate
(pH 7.8; osmolality 20 mOsm/mL) and gently mixing
until the contents were suspended. The resulting milky
white liquid was then administered by mouth. The
suspensions were freshly prepared for each administra-
tion during this study. The pH of simpli®ed omeprazole
suspension was 7.97; the pH of simpli®ed lansoprazole
suspension was 7.92.
Using a 10-cm visual analogue scale, subjects were
asked to rate the palatability of each of the four
formulations administered on day 1 and day 5. On this
scale, zero indicated the worst imaginable taste and 10
the best.
Statistical analysis
Plasma omeprazole and lansoprazole levels were tabu-
lated for each subject. Maximum plasma concentration
(Cmax) and time to Cmax (tmax) were derived from
inspection of the data. The area under the plasma
concentration/time curve (AUC) was calculated accord-
ing to the linear trapezoidal rule.
Data for tmax, Cmax and AUC were summarized as
medians and ranges, and analysed non-parametrically.
Values for tmax, Cmax and AUC with omeprazole capsules
were compared to those with simpli®ed omeprazole
suspension using the Wilcoxon matched-pairs signed-
rank test. Corresponding data for lansoprazole and
simpli®ed lansoprazole suspension were handled simi-
larly. Omeprazole data were not compared with lan-
soprazole data. Data for tmax, Cmax and AUC for each
formulation on day 1 of its administration were
compared with those on day 5 of administration. The
relative bioavailability of omeprazole from simpli®ed
omeprazole suspension and of lansoprazole from
simpli®ed lansoprazole suspension was de®ned as
AUCsuspension/AUCcapsule..7 Data on palatability between
Table 1. Summary pharmacokinetic data expressed as median (range) following omeprazole 20 mg o.d. as capsules and as simpli®ed
omeprazole suspension
Omeprazole capsules 20 mg
Day 1
tmax (h) 1.0 (0.5±6)
Cmax (ng/mL) 222 (56±676)
AUC (ng.h/mL) 197d (76±1220)
SOS, simpli®ed omeprazole suspension.
a
P = 0.03 vs. omeprazole capsules, day 1; bP = 0.041 vs. omeprazole capsules, day 1; cP = 0.034 vs. SOS, day 5; dP = 0.037 vs. SOS, day 1;
e
P = 0.003 vs. omeprazole capsules, day 1; fP = 0.013 vs. SOS, day 5.
Ó 2000 Blackwell Science Ltd, Aliment Pharmacol Ther 14, 887±892
PROTON PUMP INHIBITOR PHARMACOKINETICS 889
the suspensions and capsules were compared using the
paired Student's t-tests. All tests were two-tailed;
P-values of 0.05 or lower were considered statistically
signi®cant.
RESULTS
Each subject completed all four dosing schedules. No
adverse events were reported during dosing with
omeprazole or lansoprazole, either as intact capsules
or as suspensions. For both omeprazole and lansopraz-
ole, each subject preferred the intact capsule formula-
tion to the liquid suspension in sodium bicarbonate
(P < 0.001 for each comparison).
Omeprazole and simpli®ed omeprazole suspension
Table 1 lists the summary pharmacokinetic data for
omeprazole when given as intact capsules and as
simpli®ed omeprazole suspension. There was no signi-
®cant change in tmax between days 1 and 5 of dosing
with either omeprazole capsules or simpli®ed omepraz-
ole suspension. However, tmax on simpli®ed omeprazole
suspension was signi®cantly lower than on omeprazole
capsules at day 1 (P ˆ 0.03) but not at day 5
(P ˆ 0.075). During dosing with omeprazole capsules,
Cmax and AUC were signi®cantly higher on day 5 than
on day 1 (P ˆ 0.041 and 0.003, respectively). How-
ever, there was no signi®cant difference for Cmax or
AUC, comparing days 1 and 5 of simpli®ed omeprazole
suspension administration (P ˆ 0.388 and 0.093,
respectively).
On day 5, Cmax after standard omeprazole capsules was
signi®cantly higher than with simpli®ed omeprazole
suspension (P ˆ 0.034), although no signi®cant differ-
ence was seen on day 1 (P ˆ 0.158). AUC was higher
after standard omeprazole capsules than after simpli®ed
SOS 20 mg
Day 5 Day 1 Day 5
a
1.25 (0.5±2) 0.5 (0.5±1.5) 0.5 (0.5±1.5)
430b,c (74±1100) 172 (69±393) 198 (69±800)
454e,f (126±1423) 160 (88±838) 265 (81±1331)
890 V. K. SHARMA et al.

omeprazole suspension on day 1 (P ˆ 0.037) and day 5

DISCUSSION
(P ˆ 0.013).
The relative bioavailability (95% CI) of omeprazole Consistent with other studies, we found an increase in
from simpli®ed omeprazole suspension compared to the the degree of absorption of omeprazole when given in
capsule was 81.2% (59.1±103.3%) on day 1 and 58.4% repeated once daily doses as its standard capsule
(30.5±86.3%) on day 5. formulation.10±12 However, we did not ®nd this when
we studied the pharmacokinetics of omeprazole admin-
istered as simpli®ed omeprazole suspension. Absorption
Lansoprazole and simpli®ed lansoprazole suspension of omeprazole from this formulation was reduced in
comparison to that seen with the standard capsule
Summary data for tmax, Cmax and AUC on days 1 and 5
formulation and there was no signi®cant increase in the
of dosing with standard lansoprazole capsules and
degree of absorption seen with repeated once daily
simpli®ed lansoprazole suspension appear in Table 2.
dosing over 5 days. The AUC increased by day 5 only
There was no signi®cant change in tmax between days 1
for the standard capsule formulation of omeprazole and
and 5 of dosing with either standard lansoprazole
not for simpli®ed omeprazole suspension. The absorp-
capsules (P ˆ 0.527) or simpli®ed lansoprazole suspen-
tion of omeprazole from its standard capsule formula-
sion (P ˆ 0.102). On day 1, tmax was signi®cantly lower
tion increases progressively over the ®rst few days of
with simpli®ed lansoprazole suspension than with the
dosing because of a progressive inhibition of intragastric
standard capsule formulation (P ˆ 0.003), although no
acidity and a consequent increase in the amount of
signi®cant difference was seen between the two formu-
omeprazole that is not denatured by acid and so is
lations on day 5 (P ˆ 0.073). Between days 1 and 5 of
available for absorption. That this does not happen
dosing with standard lansoprazole capsules, no signi-
when omeprazole is administered in the form of
®cant difference was found for Cmax (P ˆ 0.695) or AUC
simpli®ed omeprazole suspension is probably explained
(P ˆ 0.638). For simpli®ed lansoprazole suspension,
on the basis of the reduced gastric antisecretory effect of
Cmax on days 1 and 5 was not signi®cantly different
simpli®ed omeprazole suspension compared to standard
(P ˆ 0.158), although there was a tendency for AUC to
omeprazole capsules, as we have previously reported.6
increase (P ˆ 0.050).
In contrast, lansoprazole was well absorbed when
On day 1, there was no signi®cant difference between
given as simpli®ed lansoprazole suspension. Cmax and
standard lansoprazole capsules and simpli®ed lansop-
AUC values after simpli®ed lansoprazole suspension
razole suspension for Cmax (P ˆ 0.695) or AUC
were comparable to those seen with the standard
(P ˆ 0.075). Similarly, for day 5, Cmax and AUC values
capsule formulation of lansoprazole. Cmax and AUC did
were similar between standard lansoprazole capsules
not progressively increase over 5 days of dosing with
and simpli®ed lansoprazole suspension (P ˆ 0.195 and
the intact capsule formulation of lansoprazole. As
1.00, respectively).
reported by others, this indicates near maximal bio-
The relative bioavailability (95% CI) of lansoprazole
availability of lansoprazole within the ®rst day of oral
from simpli®ed lansoprazole suspension compared to the
administration.13, 14 However, there was a quantita-
capsule was 67.5% (41.0±94.0%) on day 1 and 84.7%
tively smallÐthough statistically signi®cantÐincrease
(64.3±105.1%) on day 5.

Table 2. Summary pharmacokinetic data expressed as median (range) following lansoprazole 30 mg o.d. as capsules and as simpli®ed
lansoprazole suspension

Lansoprazole capsules 30 mg SLS 30 mg

Day 1 Day 5 Day 1 Day 5

a
tmax (h) 1.0 (0.5±6) 1.5 (0.5±3) 0.5 (0.5±0.5) 0.5 (0.5±3)
Cmax (ng/mL) 678 (198±1588) 810 (80±1276) 791 (303±1370) 989 (484±1412)
AUC (ng.h/mL) 1342 (206±2542) 1109 (204±2549) 906 (350±2072) 939b (459±2408)

SLS, simpli®ed lansoprazole suspension.

a
P = 0.003 vs. lansoprazole capsules, day 1; bP = 0.05 vs. SLS, day 1.

Ó 2000 Blackwell Science Ltd, Aliment Pharmacol Ther 14, 887±892

 PROTON PUMP INHIBITOR PHARMACOKINETICS
in AUC seen between days 1 and 5 of dosing with
simpli®ed lansoprazole suspension (Table 2). By day 5,
the bioavailability of lansoprazole from simpli®ed lan-
soprazole suspension was similar to that seen with the
capsule formulation.
Phillips et al. have previously studied simpli®ed omep-
razole suspension in the prevention of stress-related
gastric bleeding in critically ill patients in an intensive
care unit.15 They administered two 40 mg doses of
simpli®ed omeprazole suspension on the ®rst day
followed by a daily 20 mg dose for the duration of their
study. These patients were not comparable to those in
our previous pharmacodynamic study of simpli®ed
omeprazole suspension.6 The former were critically ill
and had a high baseline intragastric pH while our
subjects were in a stable clinical condition without any
acute disease. These differences in study subjects,
experimental conditions and dosing schedules may
explain the different ®ndings from the two studies.
Presumably, the higher dose of simpli®ed omeprazole
suspension used in the study by Phillips et al. provided
suf®cient omeprazole for adequate systemic
absorption.15 However, our studies show that there is
insuf®cient absorption of omeprazole from simpli®ed
omeprazole suspension 20 mg. At the dose of 20 mg
o.d., simpli®ed omeprazole suspension may be
inadequate for routine clinical use as an inhibitor of
intragastric acidity.
CONCLUSION
Our current study has found differences between
simpli®ed omeprazole suspension and simpli®ed lansop-
razole suspension in terms of the degree of absorption of
their respective proton pump inhibitors when given by
mouth to healthy subjects. Lansoprazole absorption
from simpli®ed lansoprazole suspension is similar to that
seen with the standard capsule formulation, while the
absorption of omeprazole from simpli®ed omeprazole
suspension is impaired. Neither simpli®ed omeprazole
suspension nor simpli®ed lansoprazole suspension had
acceptable palatability when taken by mouth. However,
this would not be of relevance if administered through a
nasogastric or gastrostomy tube. Simpli®ed lansoprazole
suspension is at least as simple to prepare as simpli®ed
omeprazole suspension and has been shown to retain
over 90% stability when refrigerated for 4 weeks or
when stored at room temperature for 2 weeks.16 In a
dose of 30 mg o.d. through a gastrostomy, simpli®ed
Ó 2000 Blackwell Science Ltd, Aliment Pharmacol Ther 14, 887±892
891
lansoprazole suspension had a profound and consistent
effect on intragastric acidity.5 Since lansoprazole is well
absorbed when given as simpli®ed lansoprazole suspen-
sion, further study of this formulation in appropriate
clinical situations is certainly justi®ed.
ACKNOWLEDGEMENT
Financial support for this study was provided by TAP
Pharmaceuticals Inc., Deer®eld, IL, USA.
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