Integrated acidity and heartburn severity determine timing of self-medication in postprandial...
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Background: Esophageal acid sensitivity has been assessed by esophageal perfusion with exogenous acid or by correlating symptoms with intraesoph- ageal acidity. Heartburn can be associated with esophageal hypersensitiv- ity. Aim: To examine esophageal acid sensitivity and response to treatment using integrated acidity and heartburn severity. Methods: In this randomized, blinded, 4-way crossover trial, postprandial esophageal pH was measured for 4.5 hours after a meal in chronic antacid- responsive heartburn (N 5 26). Heartburn severity was assessed by VAS q 15-minutes. Subjects self-medicated with placebo, 75 mg ranitidine, 420 mg calcium carbonate, or ranitidine plus calcium carbonate. Integrated acidity was calculated from cumulative, time-weighted mean acid concen- trations in mM (derived from pH each second). Integrated heartburn se- verity was calculated from VAS scores. Esophageal acid sensitivity was assessed by dividing integrated heartburn severity by integrated esophageal acidity when placebo was administered. Results: All subjects experienced significant esophageal acid exposure and postprandial heartburn. Esophageal acid sensitivity ranged from 1 to 805 showing more than 800-fold variation among 26 subjects. Ranitidine plus antacid significantly decreased integrated esophageal acidity from 5.95 6 1.70 mmol.hr/L (mean 6 SEM) to 0.46 6 0.12 and decreased integrated heartburn severity from 127 6 16 to 85 6 10 (p , 0.001). The coefficient of variation for the decrease in heartburn severity was 80%. Using linear, least-squares regression, decreased heartburn resulting from ranitidine plus antacid correlated directly with esophageal acid sensitivity (p 5 0.017). Conclusions: Marked intersubject variability in esophageal sensitivity typifies meal-induced heartburn, a phenomenon that can account for re- ported differences in therapeutic responses to acid reduction. (Supported by a grant from Warner-Lambert.) 73 Integrated acidity: A novel technique demonstrating synergy between low dose ranitidine and antacid for acid reduction and relief of meal-induced heartburn Malcolm Robinson, Sheila Rodriguez-Stanley, Arthur A. Ciociola, Jonathan Filinto, Sattar Zubaidi, Philip B. Miner, Jr., Jerry D. Gardner. Oklahoma Foundation for Digestive Research, University of Oklahoma Health Center, Oklahoma City, OK; Warner-Lambert, Morris Plains, NJ; Science for Organizations, Inc., Chatham, NJ. Background: Pathophysiology of postprandial heartburn and its treatments has not been well studied. Aim: To characterize gastroesophageal acid/heartburn following antacids and low-dose ranitidine using integrated acidity (to be contrasted with conventional analyses previously reported in Gastroenterology 2000;118: A488). Methods: Subjects (n 5 26) with chronic, antacid-responsive heartburn underwent pH monitoring for 1 hour before, during, and 4.5 hours after a meal. Heartburn severity was assessed by VAS at 15-minute intervals. Subjects randomly self-medicated with placebo, 75 mg ranitidine, 420 mg calcium carbonate, and ranitidine plus calcium carbonate. Integrated acidity was calculated from cumulative, time-weighted mean acid concentrations in mM (derived from pH each second). Results: Dosing time was 64 6 4 minutes (mean 6 SEM) pc. Antacid significantly decreased (p , 0.01) esophageal acid concentration from 3.95 6 2.12 mM (mean 6 SEM) to 0.32 6 0.17 mM beginning 90 minutes pc (30 minutes after dosing), with no effects on gastric acidity or heartburn severity. Ranitidine significantly decreased gastric acidity from 48 6 12 mM to 31 6 9 mM (p 5 0.042) beginning 150 minutes pc (90 minutes after dosing) but did not significantly alter esophageal acidity until 195 minutes pc (135 minutes after dosing) when acidity fell from 1.44 6 0.65 mM to 0.10 6 0.05 mM (p 5 0.050). Ranitidine alone did not decrease heartburn severity. Antacid plus ranitidine significantly decreased esophageal acidity (3.78 6 1.40 mM to 0.10 6 0.04 mM; p 5 0.014) and gastric acidity (20 6 9 mM to 10 6 6 mM; p 5 0.012) beginning 105–120 minutes pc (45– 60 minutes after dosing), and significantly decreased heartburn severity (p 5 0.004). Conclusions: Treatment with low dose ranitidine plus antacid is synergistic for reduction of acidity and heartburn severity. Integrated acidity provides greater precision in assessing heartburn pathophysiology heartburn and effects of low dose ranitidine and antacid. (Supported by a grant from Warner-Lambert.) 74 Integrated acidity and heartburn severity determine timing of self- medication in postprandial heartburn Malcolm Robinson, Sheila Rodriguez-Stanley, Arthur A. Ciociola, Jonathan Filinto, Sattar Zubaidi, Philip B. Miner, Jr., Jerry D. Gardner. Oklahoma Foundation for Digestive Research, University of Oklahoma Health Center, Oklahoma City, OK; Warner-Lambert, Morris Plains, NJ; Science for Organizations, Inc., Chatham, NJ. Background: Timing of self-medication for heartburn is incompletely understood; however, heartburn severity and esophageal acid exposure are likely to be involved. Aim: To use integrated measures for acidity and heartburn severity to correlate heartburn severity, esophageal acid exposure, and the time of self-medication for heartburn relief. Methods: Each subject randomly received 4 different treatments in a double-blind crossover manner (placebo, 75 mg ranitidine, 420 mg calcium carbonate, or ranitidine plus calcium carbonate). Esophageal pH was mea- sured for 4.5 hours following a refluxogenic meal in antacid-responsive heartburn (N 5 26). Postprandial heartburn was assessed by VAS q 15-minutes. Integrated acidity was calculated from cumulative, time- weighted mean acid concentrations in mM (derived from pH each second). Integrated heartburn severity was calculated from VAS scores. To corre- lations with dosing time, coefficients of variation were calculated for potential determinants of self-medication timing. Results: All subjects experienced postprandial heartburn. Dosing was 64 6 4 minutes (mean 6 SEM) pc. At dosing, the coefficient of variation was lowest for heartburn severity (33%), next for integrated heartburn severity (96%), and highest for mean esophageal acid concentration (186%) and integrated esophageal acidity (176%). Dosing with placebo occurred when mean heartburn severity and mean esophageal acid concentration were 76% and 16% of maximal, respectively. Conclusions: Subjects with meal-induced heartburn self-medicate when heartburn becomes sufficiently intense and is near peak severity. Cumula- tive heartburn severity, esophageal acid concentration or cumulative esoph- ageal acid exposure at dosing do not appear to be important determinants. (Supported by a grant from Warner-Lambert.) 75 Esomeprazole 40 mg provides more effective acid control than omeprazole 40 mg Kerstin Ro ¨hss, Christina Lundin, Hans Rydholm, Lars Nyman. AstraZeneca, Molndal, Sweden. Purpose: Esomeprazole, the S-isomer of omeprazole, is the first proton pump inhibitor developed as an optical isomer to be available for clinical use. The aim of this study was to compare the effect on intragastric pH of esomeprazole 40 mg vs omeprazole 40 mg in patients with symptomatic gastroesophageal reflux disease (GERD). Methods: In an open, randomized, two-way crossover study, 130 patients (60 males; mean age 32 years) received esomeprazole 40 mg or omeprazole 40 mg once daily in the morning for 5 days with a washout period of at least 14 days. A 24-hour intragastric pH recording was performed on Days 1 and 5 in each period. The percentage of time with intragastric pH .4 during the 24-hr period was analyzed, using a mixed model ANOVA. The mean for each treatment and the mean treatment difference were estimated with 95% CI. 2432 Abstracts AJG – Vol. 95, No. 9, 2000
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Transcript of Integrated acidity and heartburn severity determine timing of self-medication in postprandial...
Background: Esophageal acid sensitivity has been assessed by esophagealperfusion with exogenous acid or by correlating symptoms with intraesoph-ageal acidity. Heartburn can be associated with esophageal hypersensitiv-ity.Aim: To examine esophageal acid sensitivity and response to treatmentusing integrated acidity and heartburn severity.Methods: In this randomized, blinded, 4-way crossover trial, postprandialesophageal pH was measured for 4.5 hours after a meal in chronic antacid-responsive heartburn (N5 26). Heartburn severity was assessed by VASq 15-minutes. Subjects self-medicated with placebo, 75 mg ranitidine, 420mg calcium carbonate, or ranitidine plus calcium carbonate. Integratedacidity was calculated from cumulative, time-weighted mean acid concen-trations in mM (derived from pH each second). Integrated heartburn se-verity was calculated from VAS scores. Esophageal acid sensitivity wasassessed by dividing integrated heartburn severity by integrated esophagealacidity when placebo was administered.Results:All subjects experienced significant esophageal acid exposure andpostprandial heartburn. Esophageal acid sensitivity ranged from 1 to 805showing more than 800-fold variation among 26 subjects. Ranitidine plusantacid significantly decreased integrated esophageal acidity from 5.9561.70 mmol.hr/L (mean6 SEM) to 0.466 0.12 and decreased integratedheartburn severity from 1276 16 to 856 10 (p, 0.001). The coefficientof variation for the decrease in heartburn severity was 80%. Using linear,least-squares regression, decreased heartburn resulting from ranitidine plusantacid correlated directly with esophageal acid sensitivity (p5 0.017).Conclusions: Marked intersubject variability in esophageal sensitivitytypifies meal-induced heartburn, a phenomenon that can account for re-ported differences in therapeutic responses to acid reduction.(Supported by a grant from Warner-Lambert.)
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Integrated acidity: A novel technique demonstrating synergybetween low dose ranitidine and antacid for acid reduction andrelief of meal-induced heartburnMalcolm Robinson, Sheila Rodriguez-Stanley, Arthur A. Ciociola,Jonathan Filinto, Sattar Zubaidi, Philip B. Miner, Jr., Jerry D. Gardner.Oklahoma Foundation for Digestive Research, University of OklahomaHealth Center, Oklahoma City, OK; Warner-Lambert, Morris Plains,NJ; Science for Organizations, Inc., Chatham, NJ.
Background: Pathophysiology of postprandial heartburn and its treatmentshas not been well studied.Aim: To characterize gastroesophageal acid/heartburn following antacidsand low-dose ranitidine using integrated acidity (to be contrasted withconventional analyses previously reported in Gastroenterology 2000;118:A488).Methods: Subjects (n5 26) with chronic, antacid-responsive heartburnunderwent pH monitoring for 1 hour before, during, and 4.5 hours after ameal. Heartburn severity was assessed by VAS at 15-minute intervals.Subjects randomly self-medicated with placebo, 75 mg ranitidine, 420 mgcalcium carbonate, and ranitidine plus calcium carbonate. Integrated aciditywas calculated from cumulative, time-weighted mean acid concentrationsin mM (derived from pH each second).Results: Dosing time was 646 4 minutes (mean6 SEM) pc. Antacidsignificantly decreased (p, 0.01) esophageal acid concentration from3.956 2.12 mM (mean6 SEM) to 0.326 0.17 mM beginning 90 minutespc (30 minutes after dosing), with no effects on gastric acidity or heartburnseverity. Ranitidine significantly decreased gastric acidity from 486 12mM to 316 9 mM (p5 0.042) beginning 150 minutes pc (90 minutes afterdosing) but did not significantly alter esophageal acidity until 195 minutespc (135 minutes after dosing) when acidity fell from 1.446 0.65 mM to0.106 0.05 mM (p5 0.050). Ranitidine alone did not decrease heartburnseverity. Antacid plus ranitidine significantly decreased esophageal acidity(3.786 1.40 mM to 0.106 0.04 mM; p5 0.014) and gastric acidity (2069 mM to 106 6 mM; p 5 0.012) beginning 105–120 minutes pc (45–60
minutes after dosing), and significantly decreased heartburn severity (p50.004).Conclusions:Treatment with low dose ranitidine plus antacid is synergisticfor reduction of acidity and heartburn severity. Integrated acidity providesgreater precision in assessing heartburn pathophysiology heartburn andeffects of low dose ranitidine and antacid.(Supported by a grant from Warner-Lambert.)
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Integrated acidity and heartburn severity determine timing of self-medication in postprandial heartburnMalcolm Robinson, Sheila Rodriguez-Stanley, Arthur A. Ciociola,Jonathan Filinto, Sattar Zubaidi, Philip B. Miner, Jr., Jerry D. Gardner.Oklahoma Foundation for Digestive Research, University of OklahomaHealth Center, Oklahoma City, OK; Warner-Lambert, Morris Plains,NJ; Science for Organizations, Inc., Chatham, NJ.
Background: Timing of self-medication for heartburn is incompletelyunderstood; however, heartburn severity and esophageal acid exposure arelikely to be involved.Aim: To use integrated measures for acidity and heartburn severity tocorrelate heartburn severity, esophageal acid exposure, and the time ofself-medication for heartburn relief.Methods: Each subject randomly received 4 different treatments in adouble-blind crossover manner (placebo, 75 mg ranitidine, 420 mg calciumcarbonate, or ranitidine plus calcium carbonate). Esophageal pH was mea-sured for 4.5 hours following a refluxogenic meal in antacid-responsiveheartburn (N5 26). Postprandial heartburn was assessed by VAS q15-minutes. Integrated acidity was calculated from cumulative, time-weighted mean acid concentrations in mM (derived from pH each second).Integrated heartburn severity was calculated from VAS scores. To corre-lations with dosing time, coefficients of variation were calculated forpotential determinants of self-medication timing.Results:All subjects experienced postprandial heartburn. Dosing was 6464 minutes (mean6 SEM) pc. At dosing, the coefficient of variation waslowest for heartburn severity (33%), next for integrated heartburn severity(96%), and highest for mean esophageal acid concentration (186%) andintegrated esophageal acidity (176%). Dosing with placebo occurred whenmean heartburn severity and mean esophageal acid concentration were 76%and 16% of maximal, respectively.Conclusions: Subjects with meal-induced heartburn self-medicate whenheartburn becomes sufficiently intense and is near peak severity. Cumula-tive heartburn severity, esophageal acid concentration or cumulative esoph-ageal acid exposure at dosing do not appear to be important determinants.(Supported by a grant from Warner-Lambert.)
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Esomeprazole 40 mg provides more effective acid control thanomeprazole 40 mgKerstin Rohss, Christina Lundin, Hans Rydholm, Lars Nyman.AstraZeneca, Molndal, Sweden.
Purpose: Esomeprazole, the S-isomer of omeprazole, is the first protonpump inhibitor developed as an optical isomer to be available for clinicaluse. The aim of this study was to compare the effect on intragastric pH ofesomeprazole 40 mg vs omeprazole 40 mg in patients with symptomaticgastroesophageal reflux disease (GERD).Methods: In an open, randomized, two-way crossover study, 130 patients(60 males; mean age 32 years) received esomeprazole 40 mg or omeprazole40 mg once daily in the morning for 5 days with a washout period of at least14 days. A 24-hour intragastric pH recording was performed on Days 1 and5 in each period. The percentage of time with intragastric pH.4 during the24-hr period was analyzed, using a mixed model ANOVA. The mean foreach treatment and the mean treatment difference were estimated with 95%CI.
2432 Abstracts AJG – Vol. 95, No. 9, 2000
