Excretion of endogenous and exogenous purine derivatives in sheep: effect of increased concentrate intake

The scintigraphic measurement of colonic transit is currently performed using 111In ion exchange resin pellets delivered to the colon in a capsule coated with a pH sensitive polymer, methacrylate, which dissolves in the distal ileum. However, in the USA, this requires an investigational drug permit. Our aim was to evaluate the in vitro binding characteristics of activated charcoal in milieus that mimicked gastric and small intestinal content. The in vitro incubation of activated charcoal was performed with Na99Tc(m)O4, 99Tc(m)-DTPA, 111InCl3, 111In-DTPA, 201TlCl and 67Ga-citrate in the pH range 2-4 and pH 7.2 at 37 degrees C. We estimated the association of radiopharmaceuticals with the activated charcoal over a 3 h in vitro incubation. With the exception of 67Ga-citrate, the association of activated charcoal with the other radiopharmaceuticals was approximately 100% throughout the 3 h incubation. In conclusion, activated charcoal appears to adsorb avidly with common radioisotopes, and appears promising as an alternative to resin ion exchange pellets used for the measurement of gastrointestinal transit by scintigraphy.     

Simplified method for the measurement of segmental colonic transit time

Segmental colonic transit has been measured in 101 patients. Two MBq of 111Indium absorbed on resin pellets and encapsulated in an enteric coated capsule was given at 7 00 am. Hourly images during the first day, and three images during each subsequent day were acquired for up to three days. Using all scan and patient data the scans were categorised in one of the five patterns of colonic transit: normal, rapid, right delay, left delay, or generalised delay. The geometric centres and per cent activity at each time point was compared between the five groups of colonic transit patients to find the best time for imaging and so to distinguish the five groups. During the first day, early images did not help in diagnosis of patterns of transit, however, in the later images (six hours onwards after the ingestion of the activity) the rapid transit groups could be identified. Images at 27 and 51 hours were both required to distinguish all five groups of patients from each other. Only in the 'normal' transit patients was there some excretion of the activity during the course of the second day, otherwise there was no difference in the images taken in the course of a day (second or third day). A simplified protocol requires a minimum of three images to distinguish all five patterns of colonic transit. The activity should be ingested in the morning (7 00 am) and the first image taken at the end of the working day (8-10 hours after ingestion), the second image on the morning of the second day, and the third image during the course of the third day. This simple protocol would provide all the clinically relevant information necessary for correct classification of the colonic transit.     

The distal colon provides reserve storage capacity during colonic fluid overload

BACKGROUND: In addition to its absorptive function the capacity of the colon to retain fluid might be relevant in compensating for increased fluid loads and prevention of diarrhoea. The distal colon is considered to be mainly a conduit without extensive storage function. AIMS: To evaluate colonic volume capacity in a model of pure osmotic diarrhoea. METHODS: A non-absorbable, iso-osmotic solution (OS) containing polyethylene glycol (500 ml) was infused into the caecum of nine healthy volunteers; the control group (n = 5) received an equal amount of an easily absorbable electrolyte solution (ES). Fluids were radiolabelled with technetium-99m and gamma camera images were obtained for 48 hours. Counts in the proximal and distal colon were measured and regional and overall colonic transit and stool output were quantified. RESULTS: After OS, in contrast to ES, faecal output was increased significantly (p < 0.05), but colonic transit after OS was not different from transit after ES (p > 0.05). This indicates storage of OS in the colon: after OS infusion, counts in the proximal colon decreased linearly while the distal colon stored approximately 30% of radioactivity for the whole 48 hour study period. After OS, stool output correlated with distal (p < 0.01), but not with proximal (p > 0.05), colonic transit. In contrast, after ES, stool output was determined by proximal colonic transit (p < 0.05) but not by transit through the distal colon (p > 0.05). CONCLUSION: The distal colon retains non-absorbable fluid volumes extensively. In our model transit through the distal colon--but not the proximal colon--determined the time at which diarrhoea occurred.     

Left ventricular shape analysis from three-dimensional echocardiograms

Cystic fibrosis patients require pancreatic enzyme supplements to aid food digestion. It is suspected that incorrect delivery of this enzyme may result in both significant malabsorption and the development of strictures in the proximal colon caused by the high-dose supplement reaching this region before the food. Investigations into the drug's delivery were performed using dual-isotope imaging; a method was developed to directly label the enteric-coated enzyme pellets with 111In, re-applying the enteric coating afterwards, and this was then ingested with a pancake meal labelled with 99Tcm-tin colloid. Consecutive image data, acquired over a period of > or = 4 h using a dual-headed gamma camera, were analysed to assess intestinal transit. In-vitro stability checks on these labelling techniques were encouraging, showing < 2% 99Tcm and < 7% 111In elution over 90 min in hydrochloric acid. In 5 of the 12 patients studied to date, the pellets were seen to pass through significantly faster than the food, with a mean difference in 50% gastric emptying time of greater than 93 min. The mean absolute difference in emptying time for all 12 patients was > 67 min. Thus, a technique has been developed to effectively radiolabel pancreatic enzyme pellets, and analysis of dual-isotope images using this preparation, together with radiolabelled solid food, has demonstrated significant differences in the transit of these two substances through the gastrointestinal tract of some cystic fibrosis patients.     

Gastrointestinal transit in patients with idiopathic megarectum

PURPOSE: In patients with idiopathic megarectum, it is unknown whether abnormality is limited to the dilated large bowel or whether the upper gut is abnormal, as in the various forms of chronic intestinal pseudo-obstruction. This has important implications for treatment, especially surgery. METHODS: Ten patients (4 females; median age, 18 (range, 17-26) years) with idiopathic megarectum had contrast studies of the upper and lower gut, radioisotope (technetium-99m liquid and indium-111 solid phase) measurement of gastric, small-bowel, and colonic regional transit, and radiopaque marker colonic studies. RESULTS: All patients had a dilated large bowel. No patient had radiographic evidence of upper gut dilation. Four patients had normal and six patients had abnormally slow gastric emptying. Both the radioisotope scans and radiopaque marker studies showed abnormal colonic transit. Regions of delay corresponded with the region of dilated bowel. Symptoms of abdominal distention and bloating did not correspond to abnormalities of gastric emptying but rather with effectiveness of rectal evacuation. CONCLUSION: Patients with idiopathic megarectum have abnormal colonic transit, delay occurring predominantly in the dilated gut. Marker studies are less sensitive than isotope studies but provide adequate information for clinical purposes. Although motility abnormalities of the upper gut are common, symptoms correlate with large-bowel abnormalities.     

Accelerated right colonic emptying after simulated upper gut hemorrhage

OBJECTIVE: Upper gastrointestinal hemorrhage delays gastric emptying. Our aim was to evaluate the effect of gastrointestinal hemorrhage on small intestinal, ileocecal, and proximal colonic transit. METHODS: Healthy volunteers were randomized to receive either a duodenal infusion of heparinized autologous blood (n = 7) or egg white, acting as a control substance with similar composition; 1.5 mCi99mTc-DTPA was added to the infused substances. We infused 30 ml at an infusion rate of 1 ml/min. Gamma-camera images were taken for 4 h or until all radioactivity had entered the colon. Arrival of radiolabels in the colon and also counts in the ascending and transverse colon were quantified. RESULTS: Small intestinal and ileocecal transit were not significantly different between blood and egg white infusions. However, ascending colonic emptying was significantly faster after blood infusion compared to egg white. Four hours after the start of blood infusion a median of 30% of counts were in the transverse colon (11-50%; 25th-75th percentile) versus 0% (0-7%) after egg white infusion (p < 0.001). CONCLUSION: We concluded that simulated upper gastrointestinal bleeding hastens proximal colonic transit, but does not alter small intestinal transit and colonic filling.     

The influence of haemoperfusion on haemostasis and cellular constituents of the blood in the treatment of intoxications: a comparative study of three types of columns (Haemocol, Amberlite XAD-4, Gambro Adsorba 300 C)

The influence of haemoperfusion on blood-coagulation and cellular constituents of the blood was studied in three groups of patients. In four patients haemoperfusion was performed using a column containing acrylic-hydrogel coated activated charcoal (Haemocol), in five patients with a column containing uncoated XAD-4 nonionic polystyrene resin (Amberlite) and in five patients with a column containing cellulose coated activated charcoal (Gambro Adsorba 300 C). Perfusion was performed during 4 h with a flow of 300 ml/min. Before the start, 2 h after the start, at the end and 2 h after the end of the perfusion the haemoglobin concentration, haematocrit, leucocyte number, differential white cell count, thrombocyte number and heparin concentration were measured. Before the start and 2 h after the end prothrombin time, thrombin time, partial thromboplastin time, reptilase time, fibrinogen, prothrombin, factors V, VII, X, antithrombin III, bleeding time (Ivy), ethanol gelation test, fibrin split products and plasminogen were measured. The following conclusions can be drawn: haemoperfusion per se causes haemodilution; polystyrene resin causes in some patients a temporary reduction of the leucocyte number during haemoperfusion; polystyrene resin causes a significant reduction of thrombocyte number compared to coated activated charcoal; polystyrene resin and to a lesser extent acrylic-hydrogel-coated activated charcoal causes in some patients a prolongation of bleeding time probably by inducing alteration of thrombocyte function caused by release; polystyrene resin and probably also acrylic-hydrogel-coated activated charcoal causes an increased fibrinolytic activity without signs of disseminated intravascular coagulation.     

Colonic transit times and the effect of lactulose or lactitol in hospitalized patients

OBJECTIVE: To investigate whether a small dose (10 g per day) of a laxative (liquid lactulose, crystallized lactulose, or crystallized lactitol) can prevent the slow colonic transit associated with the physical inactivity of hospitalization. DESIGN: Patients were randomly allocated to one of four groups: control, liquid lactulose, crystallized lactulose or crystallized lactitol, and the average of mean colonic transit times in these groups was compared. SETTING: Gastroenterologic Unit, Hospital dos Covoes, Coimbra, Portugal. PATIENTS: Patients with normal bowel movements, admitted to hospital for the investigation of conditions not associated with constipation or diarrhoea, were allocated to one of the four treatment groups and had their mean colonic transit times studied after hospitalization using radiopaque markers and abdominal radiographs. Each study group had 18 patients. During the study, each patient was given a normal diet and no drugs except the relevant laxative. RESULTS: The average of the mean colonic transit times in each of the four groups were: 52.16 h [95% confidence interval (CI) 39.42-64.84] for controls; 22.45 h (95% CI 13.84-31.06) in the liquid lactulose group; 24.05 (95% CI 12.13-35.97) in the crystallized lactulose group; and 35.95 (95% CI 23.82-48.08) in the crystallized lactitol group. The differences were statistically significant for the two lactulose groups. The study of the mean colonic regional transit times showed that these differences related to transit in the right colon. CONCLUSIONS: A small dose of lactulose (either liquid or crystallized) was effective in preventing slow colonic transit and constipation in hospitalized patients without causing unwanted symptoms. The slow transit affected mainly the right colon, and it was in this region that the laxative had effect.     

Pilot study of pathophysiology of constipation among community diabetics

We aimed to compare gastrointestinal transit and defecatory function in a random sample of people with or without diabetes mellitus in a US community who reported constipation or laxative use. In this pilot study we measured: gastric, small bowel, and colonic transit by scintigraphy; vector manometry of anal sphincters at rest and during squeeze; defecatory dynamics by balloon expulsion test; and scintigraphic measurement of anorectal angle at rest and during defecation. Autonomic function tests were performed in diabetics. Diabetics with constipation had a higher prevalence of abnormal evacuation or prolonged colonic transit during the first 24 hr than controls (P = 0.07): three had prolonged 24-hr colonic transit, and three abnormal evacuation. Among constipated controls, only one had anismus. Overall, diabetics had slower colonic transit during the first 24 hr than nondiabetics (P < 0.05). Community diabetics who experience constipation or use laxatives have a greater prevalence of delayed 24-hr colonic transit or evacuatory dysfunction than community controls.     

Review article: issues in oral administration of locally acting glucocorticosteroids for treatment of inflammatory bowel disease

Inflammatory bowel diseases are treated in some cases by local administration of anti-inflammatory drugs. Local delivery of drugs in the colon following oral administration may lead to improved efficacy/side-effect profiles and may improve patient compliance. This review covers a number of issues important in the design of oral delivery systems of glucocorticosteroids for local therapy of colonic inflammation. The choice of specific glucocorticosteroids is based on the drug's physicochemical and pharmacological properties. The conditions under which an orally administered glucocorticosteroid (or other drug) must be delivered to treat ulcerative colitis are also discussed. These conditions include variations in local pH, transit throughout the gastrointestinal tract, the potential role of gut microflora, and drug dissolution in both the healthy and diseased large intestine. The effective delivery of topically-active glucocorticosteroids in ulcerative colitis and Crohn's colitis patients is complex, but if successful could improve their usefulness.     

Scintigraphic evaluation of experimental colitis in rabbits

Scintigraphic techniques are frequently used for evaluation of inflammatory bowel disease. The radiopharmaceutical of choice is labeled leukocytes. In this study, two new agents, 111In-labeled polyethylene glycol-coated liposomes and 111In-labeled human nonspecific gamma globulin (immunoglobulin G; IgG), were compared with 111In-leukocytes in a rabbit model of colitis. METHODS: In rabbits, acute colitis was induced by colonic instillation of trinitrobenzene sulfonic acid at 25 cm from the anal sphincter. After 24 hr, 15 MBq of the radiopharmaceuticals was injected intravenously in groups of four rabbits. Twenty-four hours after injection, the animals were killed and macroscopic abnormalities were scored in seven consecutive affected colonic segments of 5 cm each (0 = normal, 1 = inflammation, 2 = ulcers). The ex vivo uptake was measured in the normal ascending colon and the affected colonic segments. The colitis index (CI, affected-to-normal colon-uptake ratio) was calculated. RESULTS: Histologically, an acute, patchy, transmural colitis was observed at the site of instillation and the distal colon. The CI of all agents in colitis lesions correlated with the severity of the abnormalities. With increasing severity, the CI for liposomes was 1.86 +/- 0.24, 4.88 +/- 0.42 and 7.42 +/- 0.54 (r2 = 0.68, p < 0.001); for leukocytes 1.77 +/- 0.32, 3.10 +/- 0.58 and 5.54 +/- 0.83 (r2 = 0.31, p < 0.01); for IgG 1.60 +/- 0.29, 2.81 +/- 0.21 and 2.65 +/- 0.21 (r2 = 0.29, p < 0.02). CONCLUSION: Indium-111-labeled-leukocytes, -IgG and -liposomes all show increased uptake in inflamed colonic tissue. Indium-111-liposomes showed the highest CI, which correlates best with the morphological abnormalities. Indium-111-leukocytes and 111In-liposomes are superior to 111In-IgG for this indication.     

Second generation hepatitis C virus antibody-positive rate in children: investigation of the route of hepatitis C virus infection in children with no history of transfusion

BACKGROUND: Proponents of laparoscopic colectomy claim a more rapid return of gastrointestinal function, but objective data supporting this contention are lacking. Our aim was to compare the duration of delay in gastrointestinal transit after total laparoscopic, laparoscopic-assisted, and open colonic resection. METHODS: Thirty-nine female dogs were assigned to three groups: group 1, laparoscopic colectomy; group 2, laparoscopic-assisted colectomy; and group 3, open colectomy. Transit studies were performed before operation and on days 1, 2, 3, and 5 after a mid-descending colectomy with end-to-end anastomosis. Gastric emptying of liquids and small bowel transit of liquids were determined by means of radionuclide techniques. Gastric emptying of solids and colonic transit were measured by following transit of radiopaque spheres instilled into the stomach and proximal colon, respectively. RESULTS: With each dog as its own control, gastric emptying returned to preoperative values by 2 days in group 1, 3 days in group 2, and 5 days in group 3. Small bowel transit returned to preoperative values on day 3 for groups 1 and 2 and on day 5 for group 3. Gastric emptying of solids and colonic transit returned to preoperative values on day 3 for group 1 and on day 5 for groups 2 and 3. CONCLUSIONS: These observations show that laparoscopic resection techniques in this canine model resulted in a more rapid return to normal gastrointestinal transit compared with open colectomy.     

Colonic and anorectal function in constipated patients with anorexia nervosa

OBJECTIVES: Many patients with eating disorders complain of severe constipation. Previous studies have suggested that constipation in patients with anorexia nervosa may be associated with slow colonic transit. However, it is unclear whether a refeeding program will alter colonic transit in these patients. The aim of this study was to investigate colorectal function by measuring colonic transit and anorectal function in anorexic patients with constipation during treatment with a refeeding program. METHODS: We prospectively studied 13 female patients with anorexia nervosa who were admitted to an inpatient treatment unit and compared them to 20 previously studied, age-matched, healthy female control subjects. Patients underwent colonic transit studies using a radiopaque marker technique and anorectal manometry measuring anal sphincter function, rectal sensation, expulsion dynamics, and rectal compliance. Patients were studied both early (< 3 wk) and late (> 3 wk) in their admission. We restudied two patients who had slow colonic transit. All patients also underwent structured interviews. RESULTS: Four of six patients studied within the first 3 wk of their admission had slow colonic transit, defined as > 70 h (108.0 +/- 17.0 h, mean +/- SEM), on initial evaluation. In contrast, none of the seven patients studied later than 3 wk into their admission had slow colonic transit. Two of the four patients with slow transit were restudied later in their admission and were found to have normal transit times. Rectal sensation, internal anal sphincter relaxation threshold, rectal compliance, sphincter pressures, and expulsion pattern were normal in all subjects. CONCLUSIONS: Despite complaints of severe constipation, colonic transit is normal or returns to normal in the majority of patients with anorexia nervosa once they are consuming a balanced weight gain or weight maintenance diet for at least 3 wk.     

Intragastric distribution of ion-exchange resins: a drug delivery system for the topical treatment of the gastric mucosa

Previous studies by this group on freeze-dried oral dosage forms containing finely-divided ion-exchange resins revealed prolonged gastric residence and uniform distribution within the stomach. The present study was carried out to ascertain whether this was due to freeze-drying, properties of the radiolabelled ionic exchange resin, or the small dosing volume used. 99mTc-labelled cholestyramine resin was administered in two dosage forms, a freeze-dried tablet which dissolved in the oral cavity (orally dissolving tablet; ODT) and a 1.5 mL aqueous suspension. Two resin particle sizes (20-40 and 90-125 microns) were studied. Oesophageal transit and intragastric distribution and residence were followed by gamma scintigraphy. In a second study, in six subjects, gastric emptying of the water-soluble fraction of the ODT and 1.5 mL of water, was measured using 99mTc diethylenetriaminepentaacetic acid. Oesophageal transit of a water-soluble marker and resin in suspension was rapid, but the transit of the resin in the ODTs was significantly prolonged. Regardless of particle size or dosage form, the resin was evenly distributed throughout the stomach with 20-25% remaining for 5.5 h. In contrast, the water-soluble marker cleared from the stomach rapidly from both dosage forms. We suggest that oral dose forms containing finely-divided ion-exchange resins may form a useful system for topical treatment of the gastric mucosa, for example in targeting to Helicobacter pylori infection.     

Effect of YNS-15P, a new alpha-2 adrenoceptor antagonist, on stress-stimulated colonic propulsion in rats

We studied effects of a novel alpha-2 adrenoceptor antagonist, YNS-15P (N-[(2R,11bS)-9-methoxy-1,3,4,6,7, 11b-hexahydro-2H-benzoquinolizin-2-yl]-N-methylmethanesulfonami de hydrochloride), on colonic propulsion stimulated by wrap-restraint stress (WRS) or bethanechol, on normal colonic propulsion and on diarrhea induced by castor oil in rats. Alpha-2 adrenoceptor antagonists, rauwolscine and RX821002, decreased the increase in the number and weight of fecal pellets induced by WRS. YNS-15P also inhibited WRS-stimulated fecal excretion in a dose-dependent manner. A 5-hydroxytryptamine3 receptor antagonist, granisetron, trimebutine and diazepam, but not a 5-hydroxytryptamine4 receptor antagonist, GR113808, significantly inhibited WRS-stimulated fecal excretion. YNS-15P inhibited WRS-stimulated colonic transit in a dose-dependent manner. However, YNS-15P had no significant effect on normal fecal excretion and colonic transit or on bethanechol-stimulated fecal excretion. YNS-15P also failed to inhibit castor-oil-induced diarrhea. These results indicate that YNS-15P selectively inhibits WRS-stimulated colonic propulsion, and that alpha-2 adrenoceptors may be involved in stress-induced colonic motor dysfunction in fed rats.     

Validation of a new transit time ultrasound flowmeter for measuring blood flow in colonic mesenteric arteries

OBJECTIVE: To validate a transit time ultrasound flowmeter (CardioMed CM 4000) for measuring blood flow in isolated colonic mesenteric arteries. DESIGN: Experimental and clinical study. SETTING: Teaching hospital, Denmark. ANIMALS AND SUBJECTS: One female pig, and 6 patients being operated on for carcinoma of the sigmoid colon and rectum. INTERVENTIONS: Volume blood flow measured by Cardiomed CM 4000 and pump withdrawal flow recordings. MAIN OUTCOME MEASURES: Correlation between the two methods. RESULTS: There was good agreement between transit time flow recordings and pump withdrawal flow recordings (correlation coefficient of 1.0). Of the differences between the two methods, 95% were between -0.16 ml min(-1) and 1.29 ml min(-1), mean 0.57 ml min(-1), or (in percentages) 105, 95% lying between 97-115. There was also good reproducibility in transit time flow recordings, the mean difference between repeated measurements being 0.06 ml min(-1), 95% lying between -0.66 ml min(-1) and 0.78 ml min(-1). CONCLUSION: Ultrasound transit time flow recordings gave precise measurements of blood flow in isolated colonic mesenteric arteries.     

Misoprostol in the treatment of chronic refractory constipation: results of a long-term open label trial

BACKGROUND: Misoprostol is known to be effective in stimulating intestinal transit both in healthy individuals and in patients with chronic constipation when evaluated in short-term trials. The aim of this study was to determine the utility of misoprostol in the long-term management of patients with chronic refractory constipation. METHODS: Eighteen patients were offered misoprostol (600-2400 microg/day) as adjunctive therapy in an open-ended, non-blinded trial. All patients were encouraged to continue the drug for a minimum of 4 weeks, after which time the effect on bowel movement patterns was evaluated and continued use of misoprostol was offered to those patients who demonstrated a clinical benefit. RESULTS: Six patients withdrew prior to 4 weeks because of side-effects. In the 12 patients who continued the treatment and were evaluated at 4 weeks, the mean interval between bowel movement frequency had decreased from a baseline of 11.25 to 4.8 days (P = 0.0004). Eight patients continued the long-term treatment, with sustained response seen in six. In a subset of patients (n = 4) the effect of single-dose misoprostol (400 microg) was evaluated compared to healthy controls (n = 5) on post-prandial segmental colonic motility. Misoprostol augmented the colonic motility response to a meal throughout the colon, and this was significantly greater in the left versus right colonic segments (P < 0.05). CONCLUSIONS: Misoprostol can be effective as part of the long-term medical treatment of patients with chronic refractory constipation, but side-effects are observed at higher doses and can be a limiting factor. Part of misoprostol's action may be mediated through the augmentation of colonic motility, particularly of the left colon.     

Current diagnosis and treatment of leptomeningeal metastasis

A novel colon-specific drug delivery system based on a polysaccharide, guar gum, was evaluated by conducting gamma scintigraphic studies using technetium-99m-DTPA as tracer, in six healthy male human volunteers. Scintigraphs taken at regular intervals have shown that some amount of tracer present on the surface of the tablets was released in stomach and small intestine and the bulk of the tracer present in the tablet mass was delivered to the colon. The colonic arrival time of the tablets was found to be 2 to 4 h. On entering the colon, the tablets were found to be degraded in five out of six volunteers thereby releasing a larger amount of the tracer. The study clearly demonstrates that guar gum, in the form of directly compressed matrix tablets, is a potential carrier for colon-specific drug delivery.     

Environmental conditions of the causes of noncompliance with the program of mass chest x-ray examinations and the evaluation of health status of this group of population

It is often suggested that the irritable colon syndrome is a pre-diverticular condition and that patients with diverticular disease and predominant diarrhoea are in fact suffering from the irritable colon syndrome. In this study colonic motor function in diverticular disease (7 patients with predominant diarrhoea), in the irritable colon syndrome (7 patients with predominant diarrhoea) and in 8 normal subjects were compared. Patients with diarrhoea were matched for symptom score, stool weight and transit time. Slow wave electrical activity was measured by an intraluminal suction electrode and patients with the irritable colon syndrome displayed a predominant frequency at 3 cpm. This was not found in patients with diverticular disease. No myoelectrical evidence to link the two conditions was found.     

Zolpidem (Ambien): a pediatric case series

BACKGROUND: In 1993, the nonbenzodiazepine sedative-hypnotic zolpidem tartrate (Ambien) was approved for use in the US. Zolpidem has an imidazopyridine structure and possesses a rapid onset of action and a short half-life. The toxic threshold and profile have not been well established in the pediatric population. METHODS: All pediatric zolpidem exposures reported to a regional poison information center over 24 months were reviewed retrospectively from the American Association of Poison Control Centers Toxic Exposure Surveillance System data collection forms. RESULTS: Twelve pediatric zolpidem exposures were reported. Seven were unintentional (ages 20 mon-5 y) and five were intentional misuse/suicide (ages 12-16 y). The regional poison information center was contacted within 1 h in ten cases with onset of symptoms within 10 to 60 min (mean 31.6 min). One child had no effect with 2.5 mg. As little as 5 mg caused symptoms with minor outcome in six unintentional ingestions (5-30 mg). Minor to moderate symptoms were reported 1-4 h after intentional ingestions (12.5-150 mg). The duration of symptoms in the unintentional cases ranged from less than 60 min up to 4 h (mean 2.4 h) and 6-10 h (mean 7.5 h) in the intentional exposures. Treatment consisted of observation (4), syrup of ipecac (1), lavage and activated charcoal (1), activated charcoal alone (5), and unknown (1). CONCLUSION: Due to the very rapid onset of central nervous system symptoms in children, emesis is not a treatment option. Supportive care, activated charcoal in large ingestions, and observation until symptoms resolve may be sufficient in most pediatric cases.