Esophageal transit and in vivo disintegration of branded risedronate sodium tablets and two generic formulations of alendronic acid tablets: a single-center, single-blind, six-period crossover study in healthy female subjects.

BACKGROUND: Delayed esophageal transit or disintegration of oral bisphosphonate tablets before they enter the stomach may be of concern with respect to iatrogenic complications among patients receiving longterm treatment. Different formulations of generic bisphosphonate tablets meeting regulatory requirements may have substantial differences in pharmaceutical attributes from the branded product that may result in different characteristics during esophageal transit. OBJECTIVE: The primary objective of this study was to evaluate and compare esophageal transit times and in vivo disintegration of 3 bisphosphonate formulations, one branded and the others generic, that are commercially available in Canada and the United Kingdom. METHODS: This was a single-center, randomized, singleblind, 6-period crossover study in healthy postmenopausal women aged >50 years. Each subject received a single oral dose of a branded risedronate sodium 35-mg tablet and 2 generic formulations of alendronic acid 70-mg tablets (Novopharm Limited, Toronto, Canada, and Teva UK Limited, Morley, United Kingdom) in both the erect and semisupine (45 degrees ) positions. Although the products are labeled to be taken in the erect position, the semisupine position was included to simulate dosing in bedridden patients. Subjects took tablets with 30 mL of water in the morning after an overnight fast. The tablets were radiolabeled with technetium-99m ion-exchange resins to enable visualization and measurement of esophageal transit time and disintegration using a gamma camera. Dynamic scintigraphic images were obtained for a total of 10 minutes: 2 images per second for the first 30 seconds and 1 image every 15 seconds for 9.5 minutes. This was a mechanistic study and tolerability was not assessed. RESULTS: The study was conducted in 20 healthy white female subjects with a mean age of 62 years (range, 51-77 years). The effect of body position was statistically significant (P = 0.043), with the estimated hazard ratio (HR) of 0.74 indicating longer transit time in the semisupine position relative to the erect position. There was a statistically significant difference in transit time among the 3 types of tablets (P = 0.007), with the Novopharm tablet (HR = 0.59; P < 0.001) and Teva tablet (HR = 0.71; P = 0.042) having longer transit times compared with the risedronate tablet. In 4 instances, the Novopharm tablet disintegrated and dispersed in the esophagus, once in the erect position and 3 times in the semisupine position. CONCLUSIONS: In these healthy female subjects, esophageal transit was delayed when the tablets were given in the semisupine position. The branded risedronate tablet had a significantly faster transit time than the 2 generic formulations of alendronate tested.

The effects of bolus and continuous nasogastric feeding on gastro-oesophageal reflux and gastric emptying in healthy volunteers: a randomised three-way crossover pilot study.

BACKGROUND & AIMS: Nasogastric feeding may result in gastro-oesophageal reflux and, therefore, increase the risk of aspiration. This may be greater when feeds are administered via a bolus than by infusion. We aimed to measure gastric emptying time and quantify gastro-oesophageal reflux in healthy volunteers given a liquid feed via an oral bolus (OB), a nasogastric tube bolus (TB) and a nasogastric tube drip (TD). METHODS: Twelve male volunteers participated in three separate studies (OB, TB and TD) in random order, each 3 days apart. The feed consisted of 220 ml Ensure Plus (1.5 kcal/ml), labelled with 12 MBq (99m)Tc DTPA. The OB and TB were given over 5 min and the infusion rate for the TD was 55 ml/h. Gastric emptying time was measured using gamma scintigraphy. Gastro-oesophageal reflux was observed continuously until the stomach was empty, using a multichannel intraluminal impedance catheter. RESULTS: Mean (95% CI) T(50) gastric emptying times for the OB and TB studies were 41.3 (36.5-46.2) min and 36.2 (30.6-41.8) min respectively (p=0.19). The stomach emptied at a rate equal to the infusion rate in the TD studies. Median (IQR) number of reflux episodes for the OB, TB and TD studies were 4.5 (2.0-6.0), 3.0 (2.0-4.75) and 2.0 (0.25-6.25) respectively. Median (IQR) total duration of reflux for the OB, TB and TD studies were 38 (20-242), 49 (17-71) and 36 (1-125) s respectively (p=NS). CONCLUSIONS: The lack of difference in gastro-oesophageal reflux between bolus and continuous feeding indicates that in healthy volunteers both methods are equally safe with respect to the risk of aspiration.

Validity of 13C octanoic acid breath test for measurement of solid meal gastric emptying time in children.

BACKGROUND/PURPOSE: It is important to establish a physiologic range of gastric emptying (GE) in children. Gastric emptying time measured with (99)Tc-labeled solid meal (GE(Tc)) is the gold standard. Large-scale studies with GE(Tc) are ideal but not feasible because of radiation exposure. The (13)C-labeled octanoic acid breath test (GE(13C)) does not involve radiation and is suitable for large studies. The aim of this study was to validate GE(13C) with GE(Tc) and to explore whether GE(13C) could be used to establish a physiologic range of GE in children. METHOD: Twenty-five healthy children underwent simultaneous GE(Tc) and GE(13C) using a standardized solid test meal. The time taken for the stomach to empty half its content (T(1/2)(13C)) and solid lag phase (lag(13C)) for GE(13C) were computed from the fractional excretion of (13)C in expired air. T(1/2)(13C) and lag(13C) were compared with corresponding values obtained by GE(Tc). RESULT: Correlation coefficient between T(1/2)(13C) and T(1/2)(Tc) was 0.69 (P < .01; r = 0.92 if 3 outliers were omitted). Correlation coefficient between lag(13C) and lag(Tc) was 0.39 (P < .05). There was good agreement between the methods by the Bland Altman method. CONCLUSION: There is good agreement between GE(13C) and GE(Tc). GE(13C) can be safely used to establish the reference range of GE in healthy children.

Gastric emptying of solids in normal children--a preliminary report.

OBJECTIVE: The physiological range of gastric emptying in healthy children has not previously been documented. The aim of this study was to establish the range of normal gastric emptying in children aged between 5 and 10 years with a Tc 99m-labelled solid meal acceptable to most of the children. METHODS: A list of 7 child-friendly foods was compiled. Thirty-one children aged 5 to 10 years completed a questionnaire, ranking their favourite food choices. A volume survey, to decide the weight of solid meal for the study, was carried out in 20 children. After ethical approval, gastric emptying was monitored in healthy children aged 5 to 10 years with a 99mTc-labelled solid meal selected by the methodology given hereinabove. Geometric mean counts were obtained from anterior and posterior gamma camera images, and data were used to produce normal emptying curves. In each case, a T1/2 gastric emptying time (time taken to empty half the stomach contents) was calculated. RESULTS: The overall preference was a chocolate Technecrispy cake, and the volume survey suggested a 30-g weight for the study. Twenty-four subjects consumed the meal and completed the study. The mean T1/2 gastric emptying time was 107.2 minutes (2 SD; range, 54.6-159.8 minutes). CONCLUSIONS: Chocolate Technecrispy cake was acceptable to most healthy children between 5 and 10 years of age and gave mean T1/2 gastric emptying time of 107.2 minutes. This meal can now be used for paediatric patients with transit problems.

Esophageal transit of the weekly film-coated risedronate (Actonel) placebo tablet in subjects with Kyphosis.

Risedronate sodium is a pyridinyl bisphosphonate of proven effectiveness for the treatment and prevention of osteoporosis and Paget's disease of the bone. The aim of this study was to compare the esophageal transit and gastric emptying of the placebo film-coated risedronate tablet when taken with 50 or 120 mL of water in subjects with Kyphosis. A total of 23 patients with radiologically documented osteoporosis participated in a single-center, open-label, crossover gamma scintigraphy study. The mean esophageal transit times were 15.6 s (50 mL) and 12.0 s (120 mL) and the mean gastric emptying half-times were 20.5 min (50 mL) and 14.3 min (120 mL). There was no relationship between the degree of Kyphosis measured from lateral standing radiographs and the esophageal transit time. This study demonstrated that even when taken with a minimal volume of water the esophageal transit and gastric emptying of the film-coated 35 mg weekly risedronate placebo tablet was similar in kyphotic subjects to previously obtained results from healthy control subjects.