J Clin Gilttmenleml l997:24(2):65—70.
`
`-10 1997 Ltppincott—Raven Publishers. Philadelphia
`
`The Effects of Oral Doses of Lansoprazole and
`Omeprazole on Gastric pH
`
`Keith G. Tolman, M.D., Steven W. Sanders, Pharm.D., Kenneth N. Buchi, M.D.,
`Michael D. Karol, Ph.D., Dennis E. Jennings, Ph.D., and
`Gary L. Ringham, Ph.D.
`
`We compared gastric pH values after therapeutic doses of Ian-
`soprazole and omeprazole in 17 healthy adult men. The phar-
`macokinetics of the two drugs were studied. A three-way
`crossover design compared the effects on gastric pH of 15 and
`30 mg lansoprazole and 20 mg omeprazole wach given once
`daily for 5 days. Ambulatory 24-h intragastric pH levels were
`measured before dosing, afier the first and fifth doses in each
`period. and 15 days afier each dosing period, A positive rela-
`tionship between the Iansoprazole or omeprazole area under the
`curve (AUCs) and the 24-h mean pH values was found for each
`regimen. No differences in maximum concentration (C.,..,.) and
`AUC were noted from day l to day 5 for the two lansoprazole
`doses. With omeprazole, both C..m and AUC levels were greater
`on day 5, than on day I. All three regimens increased 24-h mean
`gastric pH, although 30 mg lansoprazole had the most signifi-
`cant elTect. The percentage of time that gastric pH was >3, >4,
`and >5 was also significantly higher with 30 mg Iansoprazole.
`All three regimens were associated with reversible elevations of
`serum gastrin. which more than doubled at some points. No
`clinically significant adverse events were documented.
`Key Words: Proton pump inhibitors—Lansoprazole—Omepra-
`zole Phannaeokinetics-Pharrnacodynamicsr—Gastric pH—
`Serum gastrin.
`
`Despite changing concepts about the etiology of
`peptic ulcer disease, gastric acid remains the primary
`mediator of injury, and inhibition of its secretion leads
`to ulcer healing. The most effective agents in inhibit-
`ing acid secretion are the H+/K+-ATPase, or proton
`pump,
`inhibitors, such as omeprazole and 1ansopra-
`zole. Both drugs have shown considerable efficacy in
`the treatment of duodenal and gastric ulcers as well as
`
`Received September 22. I995. Sent for revision November 7, 1995,
`Accepted November 7. 1996.
`From the University of Utah School of Medicine (K.G.T., S.W.S..
`K.N.B.), Salt Lake City. Utah; and Abbott Laboratories (M.D.K., D.EJ..
`G.L.R.). Abbott Park, Illinois. U.S.A.
`Address correspondence and reprint requests to Dr. Keith G. Tolman,
`Division of Gastroenterology, University of Utah School of Medicine.
`ARI 18 School of Medicine, 50 No. Medical Drive. Salt Lake City. UT.
`USA.
`
`gastro-esophageal reflux disease (GERD), and both
`are generally considered safe. Because of its effects on
`hepatic oxidative metabolism, however, omeprazole
`interacts with numerous other drugs and has the po-
`tential for toxicity based on these interactions. For ex-
`ample, omeprazole inhibits the hepatic metabolism of
`diazepam (1-3), carbamazepine (4), antipyrine and
`aminopyrine (5), and the R (but not the S) isomer of
`warfarin (6). Lansoprazole has shown no effect on the
`metabolism of diazepam (7), phenytoin (8), antipyrine
`(8), propranolol (9), the R or S isomers of warfarin
`(10-11), or low-dose oral contraceptives (12). Theo-
`phylline clearance is marginally increased with both
`drugs (13-14). Bioavailability of the two drugs afler
`oral dosing also appears
`to differ:
`lansoprazole
`bioavailability after oral dosing (15) is ~85% com-
`pared with 30-40% for omeprazole (16-17). This
`study was designed to compare the pharmacodynamic
`effects of lansoprazole and omeprazole and to deter-
`mine whether a correlation exists between plasma
`AUC values and 24-h gastric pH.
`
`MATERIALS AND METHODS
`
`Seventeen healthy adult men were enrolled in the study.
`Three left the study prematurely—one because of an abnormal
`laboratory test before drug administration and two for personal
`reasons after 5 days of dosing. The subjects were nonsmokers
`with a mean age of27 years (range, 1940 years), a mean height
`of 71 inches (range, 66-76 inches). and a mean weight of 173.4
`lb (range. 141-224 lb). Physical examinations, ECGs, and lab-
`oratory evaluations were nonnal at the time of entry. None of
`the subjects had a history of drug or alcohol abuse. and none
`was taking medications that might interfere with evaluation of
`the study drugs. The study was approved by the lnvestigational
`Review Board of the University of Utah, and all subjects gave
`written infonned consent before participation.
`This was a randomized, double-blind. three-way crossover
`study comparing once-daily doses of 15 and 30 mg |ansopra-
`zole and 20 mg omeprazole. The selected doses were those ap-
`
`Lupin Exh. 1025
`
`Lupin Exh. 1025
`
`

`
`66
`
`K. G. TOLMAN ETAL.
`
`proved by the U.S. Food and Drug Administration. Each treat-
`ment period lasted 5 days. with a 2-week washout period be-
`tween treatrnents. Postdosing evaluations were conducted
`14-16 days aflcr the last dose of each ueatment (hereafier re-
`fened to as l5 days post-treatment).
`Subjects were confined to the Drug Research Center at the
`University of Utah during the dosing periods. from the time be-
`fore dinner on day -3 to the morning of day 6. so that 24-h am-
`bulatory pH recordings could be made under controlled condi-
`tions. Standardized meals were given at 9:00 a.m., I200 p.m..
`and 6:00 p.m. and a snack at 9:00 p.m.. Xanthine-containing
`foods and beverages were prohibited. Study medications were
`taken at ~8:00 am. (1 h before breakfast).
`Safety evaluation included monitoring of adverse events. vi-
`tal signs. clinical laboratory results (including gastrin levels).
`physical condition. and ECGs. On each day of confinement,
`subjects were questioned about symptoms or side efi‘ects possi-
`bly related to treatment. Vital signs were recorded daily during
`confinement and again at postdosing;
`laboratory evaluations
`were done on days 1 and 6. and postdosing. interim physical ex-
`aminations were perfonned on days -2 and 5. and ECGs were
`recorded on day 5 and postdosing. Serum gastrin levels were
`measured from samples collected l h before and I h afier meals
`on days -2. I. and 5: l5 days post-treatment; and at the end of
`each 24-h gastric pH recording period (days -I, 2, and 6 and I5
`days post-treatment), Gastrin was measured using a double an-
`tibody technique (Product KGAD-2, Gastrin Double Antibody:
`Diagnostic Products Corporation. Los Angelcs. CA. U.S.A.).
`
`Pharmacodynamic Evaluation
`During each crossover period. ambulatory 24-h gastric pH
`was monitored on days -2. I. and 5 and on day I5 post-treat-
`ment. A monocrystalline antimony electrode (Syneetics Med-
`ical lnc.. lrving. TX) was positioned in the stomach before the
`start of pH recording. Electrode placement in the stomach was
`confinned by a drop in pH during introduction of the electrode.
`The electrodes were connected to a Digitrapper Mark II single-
`channel recorder (Synectics Medical
`lnc.), which was cali-
`brated before each use with buffer solutions at pH l and 7. On
`days I and 5 of each crossover period. monitoring began imme-
`diately after drug administration and continued every 4 s for 24
`h. Values were digitized and stored by the Digitrapper unit. The
`median of each I5-min period was calculated for analysis.
`
`Pharmacokinetic Evaluation
`On days I and 5 of each treatment period. blood samples
`were drawn at several time intervals: immediately before dosing
`and at 0.5. l. L5, 2. 3. 4. 6, 8, and I2 h afier dosing. Venous
`plasma samples were analyzed for lansoprazole and omeprazole
`using validated high-performance liquid chromatography meth-
`ods (IS). The following model-independent phartnacokinetic
`parameters were evaluated: individual plasma concentrations.
`peak concentration (C...,.), time to peak concentration (T..,.,.).
`and area under the plasma concentration curve (AUG; ...). Elim-
`ination half-life (ti/2) was estimated based on linear regression
`of a log-transformed concentration of the terminal phase of the
`individual plasma concentrations. Comparisons were not made
`between lansoprazole and omeprazole because clinical rather
`than identical doses were given.
`
`Statistical Analysis
`
`Gastric pH
`All statistical tests were two-tailed. with significance desig-
`nated as p S 0.05. The preregimen value was the value obtained
`
`.I (Yin Ciuxlmrnlvml. PM 24. Na. 3, I997
`
`before each treatment regimen (day -2): the postregimen value
`was that obtained l4—l6 days afler completion (day I5 post-
`treatment). The I5-min median pH values for each subject were
`used for comparison between treatment groups. Gastric pH
`variables analyzed were mean gastric pH values (calculated as
`the average of the I5-min medians) and the percentage of time
`that gastric pH was >2. >3, >4. and >5 (based on the l5-min
`medians). All gastric pH analyses were performed over the total
`24-h period as well as over
`four specified time intervals
`(0800-1300. I300-I800,
`l800—2300. and 2300-0800 h). The
`onset of action was examined similarly on an hourly basis. with
`time to effect described as the first hour in which significant
`differences from baseline were noted.
`For each evaluation day. the effects of the three regimens on
`gastric pH variables were compared with a crossover model that
`included regimen. period. sequence. and subjects within se-
`quence as factors. Within each regimen. gastric pH variables
`were compared across days using a repeated-measures model
`that included day, sequence. and subject as factors. Within the
`framework of this model. pairwise comparisons were made of
`day 1 versus preregimen, day 5 versus preregimen. day 5 versus
`day I. and day 15 post-treatment versus preregimen.
`
`Pharmacokinetics
`Analyses of variance were perfonned for lansoprazole and
`omeprazole phannacokinetic parameters. For lansoprazole. the
`following efiects were included in the model: period. subject.
`dose. day. period-by-day interaction. and dose-by-day interac-
`tion. For omeprazole. the effects included were period. subject
`nested within period. and day. The Cm, and AUC values from
`the 30-mg lansoprazole regimen were nonnalized to a l5-mg
`dose to judge dose proportionality.
`
`Relationship ofAUC to Gastric pH
`Analysis of covariance was employed to explore the relation-
`ship between 24-h average gastric pH and plasma AUC for lan-
`soprazole and omeprazole. The dependent variable was average
`pH; the covariate was the natural logarithm of AUC. For lanso-
`prazole. an analysis was perfonned for data on days I and 5
`jointly. with effects for period. day. subject. day-by-subject in-
`teraction. and separate slopes (interaction between day and
`AUC) in the initial model. The relationship between the 24-h
`average gastric pH and the plasma drug concentration AUC was
`also examined using a sigmoidal Em. model (l9—2l ).
`
`Serum Gastrin
`Gastrin values were measured l h before and alier each meal
`on day -2 (preregimen). days I and 5, and day l5 (post-treat-
`ment) for each of the three regimens. An additional measure-
`ment was obtained l4 h afler dinner. Gastrin variables analyzed
`included values at each of these time points as well as integrated
`gastrin. defined as the area under the gastrin curve from I h be-
`fore breakfast to l h afier dinner (0800-1900). as calculated by
`the trapezoidal method. Changes from preregimen serum gas-
`trin values were analyzed between and within regimens using
`the crossover and repeated-measures model, respectively.
`
`Safety
`The incidence of adverse events during each regimen. or
`within 3 days of the last dose of any regimen, were tabulated
`and grouped by the COSTART tenn and body system. Changes
`from preregimen clinical laboratory variables and vital signs
`were compared using the crossover model described for gastric
`pH; changes in ECG and results of physical examination were
`reviewed and tabulated.
`
`

`
`EFFECT OF LANSOPRAZOLE AND OMEPRAZOLE ON GASTRIC PH
`
`RESULTS
`
`Gastric pH
`Gastric pH. as shown in Fig. 1, increased signifi-
`cantly on all three regimens, but was highest on the 30-
`mg lansoprazole regimen. The dilference between the
`30-mg dose of lansoprazole and either 20 mg omepra-
`zole or 15 mg lansoprazole was statistically significant
`afier the first and fifth doses (p S 0.002). At almost all
`time points, gastric pH was significantly higher with
`the 30-mg dose of lansoprazole than with the other two
`regimens (p < 0.05). No statistically significant differ-
`ences were evident between l5 mg lansoprazole and
`20 mg omeprazole.
`Figure 2 shows the mean gastric pH over 24 h for all
`three regimens, including a combined preregimen pro-
`file (an average of the three preregimen values). Gas-
`tric pH was consistently higher with 30 mg lansopra-
`zole than with the other two regimens. Gastric pH
`remained above 3. 4. and 5 longest in the 30-mg lan-
`soprazole regimen aficr both the first and fifth dose. A
`statistically significant difference (p <0.0l) in the
`mean percentage of time pH was >3, >4. and >5 on
`day 5 was observed between 30 mg lansoprazole and
`the other two regimens (Fig. 3). Gastric pH rose more
`rapidly after 30 mg lansoprazole than after the other
`two regimens.
`Pharmaeokinetics
`
`Details of the pharmacokinetic parameters for all
`three regimens are shown in Table I. There were no
`statistically significant differences between day I and
`day 5 in Cm“, Tm“. It-'2, or AUC (Fig. 4A) for the two
`lansoprazole doses, nor was there a statistically signif-
`icant difference in dose—nonnalized Cm, and AUC for
`
`-0- Lansoprazoie 30 mg
`—I- Lansoprazole 15 mg
`'-O" omeprazole 20 mg
`
`Pre-Regimen
`
`Day 1
`
`Day 5
`
`15 Days Post
`
`FIG. 1. Mean 24-h gastric pH levels. The asterisks mark
`statistically significant differences (p 3 0.002) between 30
`mg lansoprazole and 20 mg omeprazole or 15 mg lanso-
`prazole.
`
`
`
`MeanGastricpH
`
`
`
`MeanGastricpH
`
`800
`°°sE “"5
`
`1200
`
`1600
`
`2000
`Time
`
`......... ConI>hodPn-Ropimn
`____ Lnnsoprucio 15 mg
`Lansopruoie 30 the
`
`"""""J
`
`800
`°°°““‘
`
`1200
`
`1600
`
`2000
`11m:
`
`2400
`
`400
`
`800
`
`FIG. 2. Mean gastric pH for the two lansoprazole and the
`omeprazole regimens on day 1 (A) and day 5 (B).
`
`the two regimens. For omeprazole, no statistically sig-
`nificant differences in Tm,‘ or (1,: between day l and
`day 5 were observed. Differences did exist between
`day l and day 5 results of other pharmacokinetic para-
`meters, including Cum, AUC (Fig. 4B). dose-normal-
`ized Cmax, and dose-nomialized AUC, all of which
`were higher on day 5 than on day I (p < 0.05). For both
`lansoprazole and omeprazole. a significant positive re-
`lationship was found between 24-h pH and AUC val-
`ues, that is. increased gastric pH correlated with in-
`creased AUC values. Figure 5 shows a comparison of
`the mean day 5 24-h pH plotted against AUC and in-
`cludes the regression curves obtained from the sig-
`moid Emax model.
`
`Serum Gastrin
`
`increases in serum gastrin levels from preregimen
`to day 5 were significant with all three regimens (p <
`0.05). In most instances, day 5 values were signifi-
`cantly higher than the corresponding day 1 values and
`were similar for all regimens (Table 2). Two weeks af-
`ter dosing, serum gastrin tended to return to preregi-
`
`./ (‘/In (:'rI.\'ImrnI¢'mI, lb]. 24. Nu. J. I 997
`
`

`
`K. G. TOLMANETAL.
`
`TABLE 1. Pharmacokinetic parameters for Iansoprazole and omeprazole (mean 2 SD)
`
`Tmu (h)
`
`‘I. (h)
`
`C..... (ng/ml) AUC (ng -h/ml)
`
`Cmax dose. normalized
`(ins/mll/mg)
`
`AUC dose. normalized
`(l"9' h/mll""'|9)
`
`Lansoprazole, 15 mg
`Day 1
`Day 5
`Lansoprazole. 30 mg
`Day 1
`Day 5
`Omeprazole. 20 mg
`Day 1
`Day 5
`
`1.6 2 0.7
`1.5 2 0.5
`
`1.520.3
`1.721.3
`
`1.721.3
`1.620.?
`
`1.06 2 0.43
`1.09 2 0.56
`
`3352199
`35121.31
`
`623 2 287
`723 2 323
`
`0.97 2 0.33
`0.62 2 0.32
`
`729 2 385
`217 2140
`
`1.371 2 755
`2982186
`
`0.62 2 0.32
`0.87 2 0.50
`
`217 2140
`315 2149‘
`
`298 2 186
`595 2 377‘
`
`22.33 2 13.27
`23.40 2 8.73
`
`24.30 2 12.83
`10.85 2 7.00
`
`10.85 2 7.00
`15.75 2 7.45‘
`
`41.53 2 19.13
`48.20 2 21.53
`
`45.70 2 25.17
`149029.30
`
`14.90 2 9.30
`29.75 2 18.85‘
`
`‘Statistically significantly higher than day 1 (p < 0.05).
`
`men levels; there were no statistically significant dif-
`ferences between the preregimen and postregimen gas-
`trin levels in any treatment regimen.
`Adverse Events
`
`Adverse events were reported by five subjects (31%)
`on the 15-mg Iansoprazole regimen. six (43%) on the
`30-mg Iansoprazole regimen. and six (40%) on the 20-
`mg omeprazole regimen. Events that were reported by
`two or more subjects in any treatment group included
`asthenia. headache. dizziness. and acne (two subjects
`reporting each event) on the l5-mg Iansoprazole regi-
`men; headache (six subjects) in the 30-mg Iansoprazole
`regimen: and nausea and acne (two subjects each) on
`the 20-mg omeprazole regimen. There were no clini-
`cally significant changes in physical examinations.
`ECGS. vital signs, or laboratory tests of hematology,
`chemistry. or urinalysis in any treatment regimen. One
`subject with a normal screening alanine aminotrans-
`ferase (ALT) level (27 IU/L) had elevated values (81
`IU/L) just before dosing with 15 mg Iansoprazole; on
`day 4 of the first crossover period. his ALT had in-
`creased to 224 IU/L, and he was discontinued from the
`
`El Lansoprazoie 15 mg
`I Lansoprazole 30 mg
`
`
`
`%11mo(24h)atSpecifiedpH
`
`0%
`
`study afier testing positive for hepatitis C. Another sub-
`ject had elevated AST/ALT values attributed to study
`drugs at the end of each crossover period. His pretreat-
`ment AST and ALT levels were 30 and 36 IU/L. re-
`spectively. After the fifth dose of 30 mg Iansoprazole,
`values were 57 and I08 IU/L, respectively; by the post-
`treatment examination, AST/ALT values had decreased
`to 30 and 45 IU/L, respectively.
`
`‘
`
`A. Lansoprazole
`
`Lansoprazole 15 mg. Day I
`Lansoprazole 15 mg. Day 5
`Lansoprazola 30 mg, Day I
`Lansopmzole 30 mg, Day 5
`
`Hours
`
`B. omeprazole
`
`—A— omeprazole 20 mg, Day I
`—A— omeprazole 20 mg. Day 5
`
`EB
`5o
`'5
`Eo.
`oIC
`3
`
`
`
`omeprazole(ngImL)
`
`FIG. 3. Mean percentage of time gastric pH was >3. >4,
`and >5 on day 5. The asterisks mark statistically signifi-
`cant differences (p 5 0.01) between 30 mg Iansoprazole
`and the other two regimens.
`
`.ICIirr Guvlmwrleml. lit]. N. No. 2. I997’
`
`Hours
`
`FIG. 4. Mean plasma concentrations of Iansoprazole (A)
`and omeprazole (B) on days 1 (A) and 5 (B).
`
`

`
`EFFECT OF LANSOPRAZOLE AND OMEPRAZOLE ON GASTRIC PH
`
`69
`
`Mean24HourpH
`
`0 omeprazole, Day 5
`Lansoprazote sigmoid Emax, Day 5
`----- omeprazole sigmoid Emax, Days
`
`500100015002000250030003500
`AUC
`
`FIG. 5. Day 5 mean 24-h pH versus AUC sigmoid Emax
`model.
`
`DISCUSSION
`
`Phannacokinetic parameters in our study are similar
`to data obtained from other studies for both lansopra-
`zole and omeprazole (22-24). Dose—normalized Cm,“
`and AUC values were not difierent for the two doses of
`
`lansoprazole. With omeprazole. Cm“ and AUC levels
`were significantly higher on day 5 than on day 1, an ef-
`fect also described by Clissold and Campoli-Richards
`(24), suggesting that omeprazole’s bioavailability in-
`creases with repeated administration. Because the
`study was designed as a pharmacodynamic study, and
`because we did not use equal doses of omeprazole and
`lansoprazole, we did not make a direct statistical com-
`parison of the phannacokinetic profiles of these two
`drugs; rather, our aim was to compare their effects on
`gastric pH and to detemiine whether a relationship ex-
`ists between plasma AUC and mean 24-h gastric pH.
`A positive relationship was found between AUC and
`mean 24-h gastric pH for both lansoprazole and
`omeprazole—an observation in keeping with those of
`earlier studies (25,26). Both drugs produced signifi-
`cant increases in gastric pH, although 30 mg lansopra-
`zole was more potent that either 15 mg lansoprazole or
`20 mg omeprazole, which were comparable to each
`other. Since both drugs produce irreversible inhibition
`
`TABLE 2. Mean fasting serum gastrin levels (pg/ml)“
`
`Time point
`
`15 mg
`Lansoprazole
`
`30 mg
`Lansoprazole
`
`20 mg
`Lansoprazoie
`
`of the H+/l(+-ATPase, it is likely that the higher gas-
`tric pH produced by repeated dosing represents an ac-
`cumulation of blocked enzyme and fewer functional
`proton pumps (27,28).
`Meta-analyses of several clinical studies found a
`significant correlation between the degree of acid sup-
`pression and the rate of healing in both ulcer disease
`and reflux esophagitis (29-30). For duodenal ulcer, a
`significant correlation existed for healing and degree
`and duration of gastric acid suppression. The healing
`rate increased as gastric pH and duration of acid sup-
`pression increased. The model demonstrated the im-
`portance of raising gastric pH to 3 and indicated that
`further elevation had a negligible effect. Both the du-
`ration of time (hours per day) that gastric pH was 23
`and the duration of therapy (weeks) were more impor-
`tant than further elevation of pH. In gastric ulcer, a
`correlation also existed between suppression of 24-h
`gastric acidity and healing rates after 2, 4, and 8 weeks
`of treatment, although the correlation was less marked
`than for duodenal ulcer. in reflux esophagitis, Bell et
`al. (31) reported that maintaining pH levels above 4
`was the most important factor in predicting healing
`rate. In this study, the mean time pH levels were above
`3 and 4 was significantly greater with 30 mg lanso-
`prazole than 20 mg omeprazole or 15 mg lansopra-
`zole.
`It is uncertain whether this translates to more
`
`complete healing, although it may translate to more
`rapid healing.
`The healing rate for duodenal ulcer is already close
`to 100%, but the healing rates for gastric ulcer and
`GERD could be improved. Healing rates for GERD,
`particularly resistant esophagitis, are improved with
`proton pump inhibitors, as suggested by studies indi-
`cating a relationship between healing and degree of
`acid suppression (31,32). Healing of esophageal ulcer-
`ation correlates with an increase in gastric pH rather
`than with prevention of reflux per se. in this regard,
`both omeprazole and lansoprazole have shown cfl‘i-
`cacy in the treatment of GERD (32-34). The dose-re-
`lated suppression of gastric acid observed in our study
`parallels the dose-related healing of GERD (3 l ).
`As expected, both lansoprazole and omeprazole
`caused reversible increases in serum gastrin levels.
`Serum gastrin increased more with the 30-mg dose of
`lansoprazole, in agreement with the well-known rela-
`tionship between the extent of acid inhibition and the
`extent of increase in fasting gastrin concentrations
`(25). However, no subject in the study experienced an
`increase in gastrin values more than double the upper
`limit of normal, and all values returned to the normal
`range within 15 days of discontinuing medication. The
`magnitude of changes and their return to preregimen
`levels are similar to findings of other published stud-
`
`J Clin (iaslmenleml. Pill. 24. Na. 2. I097
`
`33.7
`40.3
`52.9
`37.7
`
`41.2”
`45.3
`59.3
`32.1
`
`33.1
`42.7
`59.2
`34.6
`
`15 Days after regimen
`'1 h belore bedtime.
`‘Significantly higher tha 15 mg lansoprazole and 20 mg omeprazole (p
`s 0.05).
`
`

`
`70
`
`K. G. IULMAN ETAL.
`
`l6.
`
`l7.
`
`l8.
`
`Regardh CG. Pharmacokinetics and metabolism of omeprazole in
`man. ScandJGas!mentemI l99l:2l:(suppl ll8):99—l04.
`Ph_vsician.r ‘desk reference. 47th ed. Montvale. N.J.: Medical Eco-
`nomics Data, l993:l582-5.
`Karol MD. Grannernan GR. Alexander K. Determination of Ian-
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`ies using lansoprazole (34-37). In light of the correla-
`tion between increased gastric pH and healing of acid
`peptic ulcer disease and GERD, the results of our
`study show that, like omeprazole, lansoprazole is a po-
`tent inhibitor of acid secretion. It also is an effective
`
`treatment for duodenal ulcer, gastric ulcer, and GERD.
`
`Acknowledgment: This study was supported by a grant from
`TAP Pharmaceuticals. Deerfield. lllinois.
`
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