Administration Of Domperidone Research Articles

Interaction of glimepiride with prokinetic drugs on some of gastrointestinal functions in STZ-induced diabetic mice

AimTo investigate the effects of metoclopramide, domperidone and erythromycin on blood glucose and serum insulin levels, gastrointestinal motility and carbohydrate absorption in streptozotocin-induced diabetic mice treated with glimepiride. Design and methodsEffects of the individual as well as combined drugs were studied in diabetic mice via estimation of the blood glucose and serum insulin levels, small intestinal transit, gastric emptying, xylose and glucose absorption tests. Diabetic groups were treated with glimepiride (10mg/kg p.o.), metoclopramide (20mg/kg p.o.), domperidone (20mg/kg p.o.) or erythromycin (6mg/kg p.o.) individually or in combination. ResultsThe test prokinetic drugs metoclopramide (20mg/kg), domperidone (20mg/kg) and erythromycin (6mg/kg) were effective in decreasing small intestinal transit, enhancing gastric emptying and increasing xylose absorption from the GIT in STZ-induced diabetic mice as compared to diabetic control value. Metoclopramide or erythromycin potentiated the effect of glimepiride (10mg/kg) on blood glucose level and serum insulin level after repeated dose administration in diabetic mice. Glimepiride (10mg/kg) significantly decreased small intestinal transit and enhanced gastric emptying in diabetic mice as compared to the diabetic control group. Administration of metoclopramide, domperidone or erythromycin with glimepiride partially antagonized the action of glimepiride on small intestinal transit and gastric emptying in diabetic mice. Administration of metoclopramide, domperidone or erythromycin along with glimepiride significantly increased xylose and glucose absorption as compared to the glimepiride treated group. ConclusionUse of metoclopramide, domperidone or erythromycin with glimepiride may guard against the risk of gastrointestinal motility disturbance associated with glimepiride treated diabetic patients and may enhance the absorption of carbohydrates. The dose of glimepiride may be safely decreased when combined with erythromycin or metoclopramide.

Finding the solution for incomplete small bowel capsule endoscopy

To evaluate whether the use of real time viewer (RTV) and administration of domperidone to patients with delayed gastric passage of the capsule could reduce the rate of incomplete examinations (IE) and improve the diagnostic yield of small bowel capsule endoscopy (SBCE). Prospective single center interventional study, from June 2012 to February 2013. Capsule location was systematically checked one hour after ingestion using RTV. If it remained in the stomach, the patient received 10 mg domperidone per os and the location of the capsule was rechecked after 30 min. If the capsule remained in the stomach a second dose of 10 mg of domperidone was administered orally. After another 30 min the position was rechecked and if the capsule remained in the stomach, it was passed into the duodenum by upper gastrointestinal (GI) endoscopy. The rate of IE and diagnostic yield of SBCE were compared with those of examinations performed before the use of RTV or domperidone in our Department (control group, January 2009 - May 2012). Both groups were similar regarding age, sex, indication, inpatient status and surgical history. The control group included 307 patients, with 48 (15.6%) IE. The RTV group included 82 patients, with 3 (3.7%) IE, P = 0.003. In the control group, average gastric time was significantly longer in patients with IE than in patients with complete examination of the small bowel (77 min vs 26 min, P = 0.003). In the RTV group, the capsule remained in the stomach one hour after ingestion in 14/82 patients (17.0%) vs 48/307 (15.6%) in the control group, P = 0.736. Domperidone did not significantly affect small bowel transit time (260 min vs 297 min, P = 0.229). The capsule detected positive findings in 39% of patients in the control group and 49% in the RTV group (P = 0.081). The use of RTV and selective administration of domperidone to patients with delayed gastric passage of the capsule significantly reduces incomplete examinations, with no effect on small bowel transit time or diagnostic yield.

Ultrasonographic Evaluation of Duodenal and Cecal Motility after Administration of Different Doses of Domperidone in Donkeys (Equus Asinus).

The objective of the present study was to evaluate the effect of different doses of domperidone on duodenal and cecal motility in donkeys. Six adult donkeys (n = 6) were used in a crossover study. Domperidone was administered orally via nasogastric tube at a dose rate of 0.5, 1 and 2 mg kg-1. Duodenal and cecal contractions were evaluated by ultrasonography using a 5 MHz curved-linear transducer. Examinations were performed before administration and at 15, 30, 60, 120 and 180 minutes post-administration. There was a significant (p< 0.05) increase of duodenal contractions after 15 minutes of domperidone administration at 1 mg kg-1 and lasted until 60 minutes. The cecal contractions were also significantly increased after 15 minutes and lasted until 60 minutes at a dose rate of 1 and 2 mg kg -1 (MANOVA fit, p< 0.01; Wilks, Lambda for dose × time interaction, p < 0.05). The results of the present study indicate that 1 mg kg-1 domperidone is the most effective prokinetic dose on duodenal and cecal contraction. Domperidone may be an alternative prokinetic drug for intestinal and cecal disorders in equines.

Electrical bioimpedance gastric motility measurement based on an electrical-mechanical composite mechanism.

To introduce a bioimpedance gastric motility measurement method based on an electrical-mechanical composite concept and a preliminary clinical application. A noninvasive gastric motility measurement method combining electrogastrogram (EGG) and impedance gastric motility (IGM) test was used. Preliminary clinical application studies of patients with functional dyspepsia (FD) and gastritis, as well as healthy controls, were carried out. Twenty-eight FD patients (mean age 40.9 ± 9.7 years) and 40 healthy volunteers (mean age 30.9 ± 7.9 years) were involved. IGM spectrum was measured for both the healthy subjects and FD patients, and outcomes were compared in the FD patients before treatment and 1 wk and 3 wk after treatment. IGM parameters were obtained from 30 erosive gastritis patients (mean age 50.5 ± 13.0 years) and 40 healthy adults, and IGM and EGG results were compared in the gastritis patients before treatment and 1 wk after treatment. There were significant differences in the IGM parameters between the FD patients and healthy subjects, and FD patients had a poorer gastric motility [percentage of normal frequency (PNF) 70.8 ± 25.5 in healthy subjects and 28.3 ± 16.9 in FD patients, P < 0.01]. After 1 wk administration of domperidone 10 mg, tid, the gastric motility of FD patients was not improved, although the EGG of the patients had returned to normal. After 3 wk of treatment, the IGM rhythm of the FD patients became normal. There was a significant difference in IGM parameters between the two groups (PNF 70.4 ± 25.5 for healthy subjects and 36.1 ± 21.8 for gastritis patients, P < 0.05). The EGG rhythm of the gastritis patients returned to normal (frequency instability coefficient 2.22 ± 0.43 before treatment and 1.77 ± 0.19 one wk after treatment, P < 0.05) after 1 wk of treatment with sodium rabeprazole tablets, 10 mg, qd, po, qm, while some IGM parameters showed a tendency toward improvement but had not reached statistical significance. The electrical-mechanical composite measurement method showed an attractive clinical application prospect in gastric motility research and evaluation.

Coadministration of Domperidone Increases Plasma Levodopa Concentration in Patients With Parkinson Disease

The aim of this study was to examine the effects of the peripheral dopamine D2-receptor antagonist, domperidone, on the plasma kinetics of levodopa in patients with Parkinson disease (PD). In a randomized crossover design, 18 hospitalized patients with PD received a single dose of levodopa/benserazide, 100/25 mg, with or without domperidone, 10 mg, under fasting conditions. Plasma levodopa concentrations were determined up to 3 hours after dose administration. Mean ± SEM levodopa maximum plasma concentration (Cmax) (14.1 ± 2.9 vs 9.7 ± 1.6 μmol/L; P < 0.01), plasma concentration at 30 min (C30 min) (13.7 ± 3.0 vs 8.1 ± 2.0 μmol/L; P < 0.01), and area under the plasma concentration-time curve from 0 to 3 hours (AUC0-3 hr) (15.9 ± 3.1 vs 12.1 ± 2.4 μmol/L · hour; P < 0.05) were significantly higher after coadministration of levodopa with domperidone compared to levodopa alone. Thus, domperidone increased levodopa Cmax and AUC0-3 hr by 1.5- and 1.3-fold, respectively. There were no exacerbations of PD by concomitant domperidone administration. The results demonstrate that coadministration of domperidone increased the bioavailability of levodopa. This may be the reason for no exacerbation of PD in concomitant administration of domperidone, a dopamine D2-receptor blocker.

Antidiuretic response of a horse affected with pituitarypars intermediadysfunction to desmopressin acetate

Summary Central diabetes insipidus (DI) was diagnosed in a 20-year-old American Quarter Horse gelding that was concomitantly affected with pituitary pars intermedia dysfunction (PPID). The diagnosis of DI was supported by a positive response to administered desmopressin acetate. Diagnosis of PPID was supported by physical appearance and elevated plasma adrenocorticotropic hormone concentration following domperidone administration. The horse's physical condition improved following treatment with pergolide but long-term treatment with desmopressin was not undertaken and severe polyuria and polydipsia persisted. Desmopressin acetate appears to be useful for the diagnosis of DI in mature horses concomitantly affected with PPID.

Transfer Entropy Estimation and Directional Coupling Change Detection in Biomedical Time Series

BackgroundThe detection of change in magnitude of directional coupling between two non-linear time series is a common subject of interest in the biomedical domain, including studies involving the respiratory chemoreflex system. Although transfer entropy is a useful tool in this avenue, no study to date has investigated how different transfer entropy estimation methods perform in typical biomedical applications featuring small sample size and presence of outliers.MethodsWith respect to detection of increased coupling strength, we compared three transfer entropy estimation techniques using both simulated time series and respiratory recordings from lambs. The following estimation methods were analyzed: fixed-binning with ranking, kernel density estimation (KDE), and the Darbellay-Vajda (D-V) adaptive partitioning algorithm extended to three dimensions. In the simulated experiment, sample size was varied from 50 to 200, while coupling strength was increased. In order to introduce outliers, the heavy-tailed Laplace distribution was utilized. In the lamb experiment, the objective was to detect increased respiratory-related chemosensitivity to O2 and CO2 induced by a drug, domperidone. Specifically, the separate influence of end-tidal PO2 and PCO2 on minute ventilation before and after administration of domperidone was analyzed.ResultsIn the simulation, KDE detected increased coupling strength at the lowest SNR among the three methods. In the lamb experiment, D-V partitioning resulted in the statistically strongest increase in transfer entropy post-domperidone for . In addition, D-V partitioning was the only method that could detect an increase in transfer entropy for , in agreement with experimental findings.ConclusionsTransfer entropy is capable of detecting directional coupling changes in non-linear biomedical time series analysis featuring a small number of observations and presence of outliers. The results of this study suggest that fixed-binning, even with ranking, is too primitive, and although there is no clear winner between KDE and D-V partitioning, the reader should note that KDE requires more computational time and extensive parameter selection than D-V partitioning. We hope this study provides a guideline for selection of an appropriate transfer entropy estimation method.

Does domperidone, a D2-antagonist alter gastric emptying rates and appetite sensations in healthy adults with high-fat meal? A block-randomised, single-blind placebo-controlled study

Accelerated gastric emptying (GE) may lead to reduced satiation, increased food intake and is associated with obesity and type 2 diabetes. Domperidone is a dopamine 2 (D(2)) receptor antagonist with claims of gastrointestinal tract pro-kinetic activity. In humans, domperidone is used as an anti-emetic and treatment for gastrointestinal bloating and discomfort. To determine the effect of acute domperidone administration on GE rate and appetite sensations in healthy adults. A single-blind block randomised placebo-controlled crossover study assessed 13 healthy adults. Subjects ingested 10 mg domperidone or placebo 30 min before a high-fat (HF) test meal. GE rate was determined using the (13)CO(2) octanoic acid breath test. Breath samples and subjective appetite ratings were collected in the fasted and during the 360 min postprandial period. Gastric emptying half-time was similar following placebo (254 ± 54 min) and 10 mg domperidone (236 ± 65 min). Domperidone did not change appetite sensations during the 360 min postprandial period (P > 0.05). In healthy adults, acute administration of 10 mg domperidone did not change GE or appetite sensations following a HF test meal.

Transmucosal delivery of domperidone from bilayered buccal patches: In Vitro, Ex Vivo and In Vivo characterization

Bilayered mucoadhesive buccal patches for systemic administration of domperidone (DOM), a dopamine-receptor (D(2)) antagonist, were developed using hydroxy propyl methyl cellulose and PVPK30 as a primary layer and Eudragit RLPO and PEO as a secondary layer. Ex vivo drug permeation through porcine buccal membrane was performed. Bilayered buccal patches were developed by solvent casting technique and evaluated for in vitro drug release, moisture absorption, mechanical properties, surface pH, in vitro bioadhesion, in vivo residence time and ex vivo permeation of DOM through porcine buccal membrane from a bilayered buccal patch. Formulation DB4 was associated with 99.5% drug release with a higuchi model release profile and 53.9% of the drug had permeated in 6 h, with a flux of 0.492 mg/h/cm(2) through porcine buccal membrane. DB4 showed 5.58 N and 3.28 mJ peak detachment force and work of adhesion, respectively. The physicochemical interactions between DOM and the polymer were investigated by differential scanning calorimetry (DSC) and fourier transform infrared (FTIR) Spectroscopy. DSC and FTIR studies revealed no interaction between drug and polymer. Stability studies for optimized patch DB4 was carried out at 40°C/75% relative humidity. The formulations were found to be stable over a period of 3 months with respect to drug content, in vitro release and ex vivo permeation through porcine buccal membrane. The results indicate that suitable bilayered mucoadhesive buccal patches with desired permeability could be prepared.

α-Melanocyte—stimulating hormone and adrenocorticotropin concentrations in response to thyrotropin-releasing hormone and comparison with adrenocorticotropin concentration after domperidone administration in healthy horses and horses with pituitary pars intermedia dysfunction

To compare endogenous ACTH and α-melanocyte-stimulating hormone (α-MSH) concentrations after administration of thyrotropin-releasing hormone (TRH) and to compare ACTH concentrations after TRH administration with those following domperidone administration in healthy horses and horses with pituitary pars intermedia dysfunction (PPID). Prospective case series. 69 clinically normal horses and 47 horses with or suspected to have PPID. ACTH concentrations were measured during 108 TRH stimulation tests in 88 horses, and α-MSH concentrations were measured during 56 TRH stimulation tests in 50 horses. In 28 of these horses, ACTH concentrations after domperidone administration were measured and test results were compared. The pituitary gland was histologically examined in all horses that were euthanatized. ACTH and α-MSH concentrations increased in all horses after TRH administration, with a greater and more prolonged increase in horses with PPID. Percentage increase was significantly greater for α-MSH concentration than for ACTH concentration. The change in ACTH concentration after domperidone administration was less consistent in differentiating clinically normal horses from those with PPID than was the response to TRH. Results suggested that ACTH concentration in response to TRH administration was useful for the diagnosis of PPID in horses and appeared more accurate than response to domperidone administration. Use of an α-MSH concentration ≥ 30 or 50 pmol/L did not appear superior to use of an ACTH concentration ≥ 36 pg/mL for the diagnosis of PPID, either before or 30 minutes after TRH administration.

Model-based characterization of ventilatory stability using spontaneous breathing

Cyclic ventilatory instabilities are widely attributed to an increase in the sensitivity or loop gain of the chemoreflex feedback loop controlling ventilation. A major limitation in the conventional characterization of this feedback loop is the need for labor-intensive methodologies. To overcome this limitation, we developed a method based on trivariate autoregressive modeling using ventilation, end-tidal Pco(2) and Po(2); this method provides for estimation of the overall "loop gain" of the respiratory control system and its components, chemoreflex gain and plant gain. Our method was applied to recordings of spontaneous breathing in 15 anesthetized, tracheostomized, newborn lambs before and after administration of domperidone (a dopamine D(2)-receptor antagonist that increases carotid body sensitivity). We quantified the known increase in hypoxic ventilatory sensitivity in response to domperidone; controller gain for O(2) increased from 0.06 (0.03, 0.09) l·min(-1)·mmHg(-1) to 0.09 (0.08, 0.13) l·min(-1)·mmHg(-1); median (interquartile-range). We also report that domperidone increased the loop gain of the control system more than twofold [0.14 (0.12, 0.22) to 0.40 (0.15, 0.57)]. We observed no significant changes in CO(2) controller gain, or plant gains for O(2) and CO(2). Furthermore, our estimate of the cycle duration of periodic breathing compared favorably with that observed experimentally [measured: 7.5 (7.2, 9.1) vs. predicted: 7.9 (7.0, 9.2) breaths]. Our results demonstrate that model-based analysis of spontaneous breathing can 1) characterize the dynamics of the respiratory control system, and 2) provide a simple tool for elucidating an individual's propensity for ventilatory instability, in turn allowing potential therapies to be directed at the underlying mechanisms.

Domperidone and Long QT Syndrome

Domperidone is a prokinetic agent widely prescribed in adults and children with gastrointestinal disorders. Recently several Regulatory Agencies published safety information on the risk of long QT syndrome associated with the use of domperidone. We conducted a literature review using PubMed (1966 - Jan 2010) with the aim to locate articles on ventricular arrhytmias, Sudden Cardiac Death (SCD), long QT syndrome and Torsade de Pointes (TdP) following domperidone administration. Twenty-two papers were included in the review: three studies in vitro models, one animal study, five case reports/series, twelve clinical studies and one editorial. In vitro studies demonstrated cardiac electrophysiological effects of domperidone on the rapid component of the cardiac delayed rectifier K(+) current (I(Kr)) through the blockade of channels encoded by the Human Ether-a-go-go Related Gene (HERG). A total of fourteen cases of cardiotoxicity following intravenous (12 cases) or oral (2 cases) domperidone administration from case reports/series were identified. A case - control study, performed on a general practice observational database reported an OR: 3.8 (95% CI: 1.5-9.7) for SCD after domperidone exposure. Prescribers and other healthcare professionals should take into account the risk of QT syndrome in domperidone users and avoid administering domperidone in patients concomitantly taking strong CYP3A4 inhibitors or other QT prolonging drugs.

Effects of domperidone on digital laminar microvascular blood flow in clinically normal adult horses

To determine effects of domperidone and acepromazine maleate on microvascular blood flow in digital laminae of clinically normal adult horses. 8 clinically normal adult horses (4 mares and 4 geldings). In a 4-period crossover study, domperidone was administered PO at 1.1 mg/ kg and 5.5 mg/kg and IV at 0.2 mg/kg; acepromazine was administered IV at 0.04 mg/kg. The washout period between treatments was 1 week. A 3-minute measurement of laminar microvascular blood flow (LMBF) was obtained with laser Doppler flowmetry. Baseline measurements were obtained at -2, -1, and 0 hours prior to administration of drugs. Post-treatment measurements were obtained at 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 10, and 12 hours. Percentage change from baseline values in LMBF for each treatment was subsequently calculated. Oral administration of domperidone at 1.1 mg/kg and 5.5 mg/kg significantly increased LMBF, compared with baseline values, beginning 4 hours after administration, and this effect persisted for at least 8 hours. Intravenous administration of domperidone at 0.2 mg/kg significantly increased LMBF, compared with baseline values, at 10 and 12 hours after administration. Administration of acepromazine (0.04 mg/kg, IV) significantly increased LMBF, compared with baseline values, at 3, 5, 8, and 10 hours after administration. No adverse effects of drugs were detected in any horse. Domperidone may be useful for preventing vasoconstriction and reduction in LMBF believed to occur in horses with laminitis, but additional research of the drug's effects in horses with laminitis is required.

Prolactin and LH responses to estradiol cypionate followed by sulpiride or domperidone administration in winter

Prolactin and LH responses to estradiol cypionate followed by sulpiride or domperidone administration in winter

Gastric Emptying of Preterm Neonates Receiving Domperidone

Objectives: Immature gut motility in very low birth weight infants causes feeding intolerance. We evaluated the effect of domperidone, a prokinetic agent, on gastric emptying in very low birth weight infants. Methods: The study was conducted in a crossover design. Gastric emptying was assessed ultrasonographically by measuring the time it took the antral cross sectional area of the stomach to reach half of the value of the 1st measurement on 2 occasions: (1) upon administration of domperidone (0.3 mg/kg/8 h p.o.) for at least 2 days and (2) while patients received an equal quantity of sterile water. 11 infants were randomly assigned to receive domperidone before the 1st measurement and the remaining afterwards. There was a 3–5 day interval between the 2 measurements. At the time when both measurements were performed, every neonate had been receiving the same quantity and quality of milk. 12 infants were formula-fed while 10 were fed their own mother’s supplemented milk. Results: 22 infants with a mean (SD) birth weight of 1,377 g (319) and a mean (SD) gestational age of 30.2 weeks (2.1) were studied. The mean (SD) antral cross sectional area half-value time (in minutes) was 47.6 (23.9) in the domperidone group and 68.2 (25.5) in the control group (p = 0.008). There was no significant difference between formula-fed neonates and neonates fed their own mother’s milk in either group. Conclusions: Domperidone significantly reduces gastric emptying in preterm neonates, and this may account for its effect in cases of disturbances related to gut motility.

Administration of sulpiride or domperidone for advancing the first ovulation in deep anestrous mares

Since results with using sulpiride and domperidone are conflicting and since both have not been tested at the same time, the aim of this study was to compare the efficacy of these substances for the induction of ovulation in deep anestrous mares in the same experimental conditions and to determine their fertility after artificial insemination (AI) at the induced estrus. Twenty-six non-pregnant, non-lactating standardbred anestrous mares were randomly assigned to three groups and treated daily for 25 days (from February 3rd to February 28th) with either sulpiride (1 mg/kg of body weight im SID, n = 10), or domperidone (1 mg/kg po SID, n = 10); 6 animals were used as control. The beginning of the transition period and the first ovulation were hastened in sulpiride (16.4 ± 0.8 days) but not in domperidone (46.0 ± 3.3 days) treated mares ( P < 0.05). The diameter of the largest follicle was affected by treatment, time and interaction of treatment-by-day ( P < 0.05) and significantly increased in the sulpiride group ( P < 0.05). Although a main effect of treatment on plasma LH concentration was not observed ( P = 0.06), time and interaction of treatment-by-day were statistically significant ( P < 0.05). The interval from the beginning of treatment to first ovulation was shorter ( P < 0.05) in the sulpiride group (36.9 ± 2.5 days) than in the domperidone (74.7 ± 3.3 days) and control (81.4 ± 3.1) groups. The establishment of pregnancy was significantly ( P < 0.05) hastened in sulpiride (61.0 ± 35.2 days) but not in domperidone (83.0 ± 44.0 days) treated mares. Treated mares not pregnant after the first AI, showed normal estrous cycles with regular interovulatory intervals ( P > 0.05). It was concluded that sulpiride is effective in advancing the beginning of transition period and the first ovulation whereas domperidone is successful only in some mares.

Effect of Domperidone on QT Interval in Neonates

To determine whether oral domperidone is associated with QT interval prolongation and ventricular arrhythmia and to identify factors that can influence these effects. An electrocardiogram was performed before and after oral administration of domperidone in 31 neonates or infants classified into 3 groups according to gestational age. Oral domperidone is associated with QTc prolongation except in infants with a gestational age less than 32 weeks of amenorrhea (P < .005). Mean QTc prolongation was 14 msec. On univariate analysis, oral domperidone-induced QTc prolongation was correlated with gestational age, birth weight, and elevated serum potassium. On multivariate analysis, after adjustment for gestational age, serum potassium was the only factor independently associated with interval QT prolongation during treatment. No ventricular arrhythmias were observed. This study shows a significant association between oral domperidone therapy and QTc prolongation. Two risk factors were identified: advanced gestational age and serum potassium at the upper limit of normal. It is recommended that measurement of the QT interval be done before and after oral domperidone therapy.

Correlation of Pituitary Histomorphometry with Adrenocorticotrophic Hormone Response to Domperidone Administration in the Diagnosis of Equine Pituitary Pars Intermedia Dysfunction

Functional evaluation of the pars intermedia (PI) is required for the early diagnosis of equine pituitary PI dysfunction (PPID), yet most assays target the hypothalamic-pituitary-adrenal axis, which regulates the pars anterior. In contrast, the PI is regulated by dopaminergic tone from hypothalamic neurons. Loss of dopaminergic inhibition is hypothesized to cause the PI hypertrophy and hyperplasia that result in the clinical manifestations of PPID. Domperidone, a dopamine receptor antagonist, should exacerbate the loss of dopaminergic inhibition in horses with PPID and increase the release of endogenous adrenocorticotrophic hormone (eACTH) by PI melanotrophs. To test this, plasma eACTH concentration was determined in horses with or without clinical signs of PPID at 0, 4, and 8 hours after oral administration of 3.3 mg domperidone/kg. Pituitary glands were evaluated postmortem by histologic grading and morphometry. In the 33 horses, median age, plasma ACTH concentration 8 hours after domperidone, and PI area in median sagittal sections were associated with histologic grade as follows: pituitary grade 1 (normal), n = 3, 7.5 years, 20.0 pg/ml, 0.16 cm(2); grade 2 (focal hypertrophy or hyperplasia), n = 9, 14.5 years, 27.1 pg/ml, 0.27 cm(2); grade 3 (diffuse adenomatous hyperplasia), n = 5, 21.0 years, 64.4 pg/ml, 0.48 cm(2); grade 4 (microadenomas), n = 12, 23.3 years, 128.0 pg/ml, 0.87 cm(2); grade 5 (adenoma), n = 4, 24.9 years, 720.5 pg/ml, 2.1 cm(2). Results suggest that horses with pituitary histologic grade > or =3 respond to domperidone with increased plasma ACTH concentration.

Influence of omeprazole on pharmacokinetics of domperidone given as free base and maleate salt in healthy Chinese patients

To investigate the influence of omeprazole on the pharmacokinetics of domperidone given as free base and maleate salt. An open, randomized, 2-period crossover study with a washout period of 7 d was conducted in 10 healthy Chinese, male patients. In each study period, the patients were administered a single oral dose of 10 mg domperidone as free base or maleate salt on d 1, 20 mg omeprazole twice daily on d 2 and 3, and once on d 4. A single dose of 10 mg domperidone as free base or maleate salt was taken at 4 h after administration of omeprazole on d 4. Plasma samples were collected on d 1 and 4 after the administration of domperidone, and the plasma concentrations of domperidone were determined by a sensitive liquid chromatography-tandem mass spectrometry method. For free-base domperidone, pretreatment with omeprazole resulted in a 16% decrease in maximum concentration (C(max)), compared with administration alone (P<0.05). However, for maleate salt, with the exception of an increase in t(1/2), no pharmacokinetic parameters were significantly changed. When the free base and maleate salt were administered alone, no differences were found in any parameters between the 2 formulations. In contrast, when they were administered in the presence of omeprazole, the C(max) of domperidone given as free base was lower (25.9%) than that given as maleate salt (P<0.05). Pretreatment of omeprazole does not affect the absorption of domperidone maleate, but leads to a moderately decreased rate of absorption of the free base.

A new tactic to treat postprandial hyperlipidemia in diabetic rats with gastroparesis by improving gastrointestinal transit

Improvement of gastrointestinal transit was thought to be a new tactic to treat postprandial hypertriglyceridemia in diabetic individuals with gastroparesis. Diabetic gastroparesis, lipid load testing, and the effect of domperidone or aqueous extract of rhizomes of Rheum palmatum L. on postprandial hypertriglyceridemia were evaluated in alloxan-induced diabetic rats. Alloxan diabetic animals had a slow gastrointestinal transit, together with delayed and exaggerated postprandial hypertriglyceridemia, after oral administration of olive oil, which was significantly improved after oral administration of domperidone or R. palmatum L. However, atropine could prevent the effects of R. palmatum L. The reduced postprandial hypertriglyceridemia was highly correlated with the improvement in gastrointestinal transit. These results suggest that promotion of gastrointestinal transit may be useful for the treatment of postprandial hypertriglyceridemia in diabetic patients with gastroparesis. R. palmatum L. may become a new choice for these patients since it has more potential benefits than domperidone.