The management of inflammatory bowel disease continues to evolve, with the introduction of biologic and small molecule therapies and new goals of treatment, with an emphasis on healing the bowel. My career goal since my graduation from IBD fellowship in 2012 has been to improve the outcomes and quality of life of patients with inflammatory bowel disease. In line with these goals, my research has focused investigating new noninvasive diagnostic test, finding factors early in the disease course that might predict a more aggressive disease course and need for different therapies, and investigating new promising effective medications with less side effects.
- Inflammatory Bowel Disease
- Ulcerative Colitis
- Crohn's Disease
- Microscopic Colitis
- Autoimmune Enteropathy
- abdominal pain
- Endoscopy, Digestive System
Clinical Associate Professor, Medicine - Gastroenterology & Hepatology
Clinical Director, Inflammatory Bowel Disease, Stanford School of Medicine (2020 - Present)
Board Certification: American Board of Internal Medicine, Gastroenterology (2022)
Medical Education: University of California at San Francisco School of Medicine (2005) CA
Residency: University of Michigan Health System Internal Medicine Residency (2008) MI
Fellowship: USC Gastrointestinal and Liver Diseases Fellowship (2011) CA
Fellowship: University of Chicago Advanced Inflammatory Bowel Disease Fellowship (2012) IL
Pentosan Polysulfate-Associated Dysplasia in Patients With Inflammatory Bowel Disease: A Case Series.
The American journal of gastroenterology
INTRODUCTION: This study evaluates the potential association of pentosan polysulfate (PPS) with inflammatory bowel disease (IBD) or dysplasia.METHODS: We searched electronic medical records to identify patients with IBD using PPS.RESULTS: Ten of 30 identified patients (33.3%) had colonic dysplasia. Six of them (60%) underwent colectomy for endoscopically unresectable dysplasia. Three (10%) discontinued PPS, each with an apparent benefit.DISCUSSION: Patients with IBD at 2 institutions who had taken PPS had high rates of colonic dysplasia leading to surgery. Patients who stopped PPS showed improvement in their colitis. PPS may play a causal role in the development of colitis and dysplasia.
View details for DOI 10.14309/ajg.0000000000002137
View details for PubMedID 36689730
Rates and Predictors of Long-term Clinical Outcomes in Patients With Perianal Crohn's Disease on Biologic Therapy.
Journal of clinical gastroenterology
Perianal Crohn's disease (pCD) represents an aggressive phenotype with limited studies on long-term outcomes. We evaluated 5-year outcomes of these patients on biologic therapies.We performed a retrospective analysis of patients with pCD at a tertiary medical center. We used Kaplan-Meier curves to estimate rates and multivariate logistic regression to identify predictors of long-term outcomes.We included 311 patients with pCD of which 168 patients were started on biologics [138 anti-tumor necrosis factor (TNF) α, 14 vedolizumab, 16 ustekinumab] at the time of diagnosis. Anti-TNF use at the time of diagnosis was associated with decreased rates of perianal abscess recurrence [hazard ratio (HR)=0.48, 95% confidence interval (CI): 0.32-0.74], whereas ustekinumab use was associated with increased rates of perianal fistula closure (HR=3.58, 95% CI: 1.04-12.35) and decreased rates of perianal abscess recurrence (HR=0.20, 95% CI: 0.07-0.56) at follow-up. Among patients who failed their first anti-TNF, switching to another anti-TNF was associated with decreased rates of colectomy (HR=0.20, 95% CI: 0.04-0.90) and permanent diversion (HR=0.16, 95% CI: 0.03-0.94) compared with ustekinumab, whereas vedolizumab use was associated with decreased perianal fistula closure (HR=0.22, 95% CI: 0.05-0.96) compared with ustekinumab. Predictors of colectomy included colonic disease (odds ratio=2.71, 95% CI: 1.36-5.38) and anal stenosis (odds ratio=4.44, 95% CI: 1.59-12.43).Type of biologic use at the time of pCD diagnosis or after first anti-TNF failure may be associated with long-term outcomes in patients with pCD.
View details for DOI 10.1097/MCG.0000000000001729
View details for PubMedID 35703262
Biologic Therapy in Patients With Perianal Crohn's Disease and Association With Long-Term Rates of Surgical and Clinical Outcomes
LIPPINCOTT WILLIAMS & WILKINS. 2021: S354
View details for Web of Science ID 000717526101241
Anti-Integrins for the Treatment of Inflammatory Bowel Disease: Current Evidence and Perspectives.
Clinical and experimental gastroenterology
2021; 14: 333-342
Leukocyte trafficking to the gastrointestinal tract is recognized to play a role in the pathogenesis of inflammatory bowel disease (IBD). Integrins are expressed on immune cells and interact with cell adhesion molecules (CAM) to mediate leukocyte trafficking. Blockade of the gut-tropic integrin α4β7 and its subunits has been exploited as a therapeutic target in IBD. Natalizumab (anti-α4) is approved for moderate to severe Crohn's disease (CD), but its use is limited due to potential risk of progressive multifocal leukoencephalopathy. Vedolizumab (anti-α4β7) is approved for the treatment of ulcerative colitis (UC) and CD. It is the most widely used anti-integrin therapy in IBD and has been shown to be effective in both induction and maintenance therapy, with a favorable safety profile. Several models incorporating clinical, genetic, immune, gut microbial, and vitamin D markers to predict response to vedolizumab in IBD have been developed. Etrolizumab (anti-β7) blocks leukocyte trafficking via α4β7 and cell adhesion via αEβ7 integrins. Large phase 3 clinical trials evaluating efficacy of etrolizumab in the induction and maintenance of patients with IBD are underway. Other investigational anti-integrin therapies include abrilumab (anti-α4β7 IgG2), PN-943 (orally administered and gut-restricted α4β7 antagonist peptide), AJM300 (orally active small molecule inhibitor of α4), and ontamalimab (anti-MAdCAM-1 IgG).
View details for DOI 10.2147/CEG.S293272
View details for PubMedID 34466013
View details for PubMedCentralID PMC8402953
Thiopurine Monotherapy Is Effective in Maintenance of Mild-Moderate Inflammatory Bowel Disease.
Digestive diseases and sciences
BACKGROUND: Crohn's disease (CD) and ulcerative colitis (UC) are complex, inflammatory bowel diseases (IBD) with debilitating complications. While severe IBD typically requires biologic agents, the optimal therapy for mild-moderate IBD is less clear.AIMS: To assess the efficacy of thiopurine monotherapy for maintenance of mild-moderate IBD and clinical variables associated with treatment outcome.METHODS: This retrospective study included adults with mild-moderate IBD who were started on thiopurines without biologic therapy. The primary outcome was therapy failure, defined by disease progression based on clinical, endoscopic, and radiologic criteria. Clinical variables were extracted at time of thiopurine initiation. Univariable and multivariable Cox proportional hazards models were used to examine the independent contribution of the clinical variables on treatment response.RESULTS: From 230 CD patients, 64 (72%) were free of treatment failure with mean follow-up of 3.3years. In our multivariable model, thiopurine failure was associated with concomitant systemic steroid administration (aHR 2.43, p=0.001), whereas protective factors included concomitant oral 5-aminosalicylic acid (5-ASA) therapy (aHR 0.54, p=0.02) and non-fistulizing, non-stricturing disease (aHR 0.57, p=0.047). From 173 UC patients, 50 (71%) were free from treatment failure with mean follow-up of 3.3years. On multivariable analysis, concomitant oral steroids were associated with thiopurine failure (aHR 2.71, p=0.001). Only 13 (4%) discontinued thiopurines from adverse effects.CONCLUSIONS: In mild-moderate uncomplicated IBD, thiopurine monotherapy was associated with longitudinal maintenance of remission and may represent a lower-cost, convenient, and effective alternative to biologics. Multiple clinical variables were predictive of treatment response.
View details for DOI 10.1007/s10620-021-06947-x
View details for PubMedID 33755823
- Anti-Integrins for the Treatment of Inflammatory Bowel Disease: Current Evidence and Perspectives CLINICAL AND EXPERIMENTAL GASTROENTEROLOGY 2021; 14: 333-342
- Comparative Incidence of Inflammatory Bowel Disease in Different Age Groups in the United States INFLAMMATORY BOWEL DISEASES 2019; 25 (12): 1983–89
- Mass Transition: From Cecal Mass to Small Bowel Ischemia. Digestive diseases and sciences 2019
Prevalence and Outcomes of Chronic Hepatitis B and C in Hospitalized Patients With Inflammatory Bowel Disease
NATURE PUBLISHING GROUP. 2018: S1557–S1558
View details for Web of Science ID 000464611005356
Protein-Calorie Malnutrition Reduces the Durability of Biologic Therapy in Inflammatory Bowel Disease
NATURE PUBLISHING GROUP. 2018: S356–S357
View details for Web of Science ID 000464611001221
Gender disparities in gastroenterology fellowship director positions in the United States.
Despite a paucity of women occupying leadership positions in academic medicine, studies have shown a higher ratio of female representation in the program director position compared with division chief in multiple specialties. This study aims to determine whether this trend exists in 3-year gastroenterology fellowships in the United States and to evaluate for any factors that may affect these differences.In 2015, data were collected for the 163 U.S. gastroenterology fellowship programs including program director, associate program director, division chief, gender distribution, program size, academic center affiliation, and geographic region.A higher percentage of men than women held the role of program director (82% vs 18%), associate program director (72% vs 28%), and division chief (93% vs 7%). Women in program leadership held lower academic rank than their male counterparts (P < .0001). The program director was more likely to be female if the division chief also was female (P = .03). Programs with a higher number of trainees tended to be led by a female program director (P = .06).A gender disparity exists in all gastroenterology leadership roles, although the magnitude is smaller for program director and associate program director than the role of division chief. Further studies are needed to investigate the impact of this disparity on promotion and academic productivity.
View details for DOI 10.1016/j.gie.2017.01.019
View details for PubMedID 28153570
- A Model for Identifying Actionable Findings on Computed Tomography in Crohn’s Disease Patients in the Emergency Department Journal of Digestive Disorders and Diagnosis 2017; 1 (3)
- Uses and limitations of IgG4 positive plasma cells in evaluating ulcerative colitis. Journal of gastrointestinal and liver diseases : JGLD 2017; 26 (4): 428–29
The role of a nurse telephone call to prevent no-shows in endoscopy
2016; 84 (6): 1010-?
Preventing missed appointments, or "no-shows," is an important target in improving efficient patient care and lowering costs in gastrointestinal endoscopy practices. We aimed to investigate whether a nurse telephone call would reduce no-show rates for endoscopic appointments, and to determine if hiring and maintaining a nurse dedicated to pre-endoscopy phone calls is economically advantageous. Our secondary aim was to identify predictors of no-shows to endoscopy appointments.We hired and trained a full-time licensed nurse to make a telephone call to patients 7 days before their scheduled upper endoscopy or colonoscopy. We compared this intervention with a previous reminder system involving mailed reminders. The effect of the intervention and impact of other predictors of no-shows were analyzed in 2 similar preintervention and postintervention patient cohorts. A mixed effects logistic regression model was used to estimate the association of the odds of being a no-show to the scheduled appointment and the characteristics of the patient and visit. An analysis of costs was performed that included the startup and maintenance costs of the intervention.We found that a nurse phone call was associated with a 33% reduction in the odds of a no-show visit (odds ratio, 0.67; 95% confidence interval, 0.50-0.91), adjusting for gender, age, partnered status, insurer type, distance from the endoscopy center, and visit type. The recovered reimbursement during the study period was $48,765, with net savings of $16,190 when accounting for the maintenance costs of the intervention; this resulted in a net revenue per annum of $43,173.We found that endoscopy practices may increase revenue, improve scheduling efficiency, and maximize resource utilization by hiring a nurse to reduce no-shows. Predictors of no-shows to endoscopy included unpartnered or single patients, commercial or managed care, being scheduled for colonoscopy as opposed to upper endoscopy, and being scheduled for a screening or surveillance colonoscopy.
View details for DOI 10.1016/j.gie.2016.05.052
View details for Web of Science ID 000389611900021
View details for PubMedID 27327847
- Novel Topics in Inflammatory Bowel Disease BIOMED RESEARCH INTERNATIONAL 2016
Prevalence of Antibodies Against JC Virus in Patients With Refractory Crohn's Disease and Effects of Natalizumab Therapy
CLINICAL GASTROENTEROLOGY AND HEPATOLOGY
2015; 13 (11): 1919-1925
Natalizumab, a humanized antibody against the α4 integrin subunit, effectively induces and maintains remission in patients with Crohn's disease (CD) refractory to conventional treatments. Progressive multifocal leukoencephalopathy is a rare but fatal brain infection caused by John Cunningham (JC) virus and has been associated with natalizumab use. We assessed the prevalence of and risk factors for antibodies to JC virus in serum of patients with refractory CD who were candidates for, or already were receiving, natalizumab. We also assessed the effects of natalizumab treatment of these patients.In a retrospective study, we analyzed clinical charts from 191 patients with CD (74 males; mean age, 38.7 y; mean duration of disease, 14.9 y) tested for serum JC virus antibody from December 2012 through May 2014 at 2 medical centers in the United States. We calculated JC virus antibody prevalence and compared the characteristics of patients who tested negative vs those who tested positive, to identify risk factors. We also assessed the rate of subsequent natalizumab use, surgery, and seroconversion during natalizumab therapy.A total of 129 of the patients (67.5%) tested positive for serum JC virus antibody. Multivariate analysis showed that past use of thiopurine was a risk factor for testing positive for JC virus antibody (odds ratio, 7.8; 95% confidence interval, 2.0-30.4; P = .003). Twenty-two of the patients who tested negative for JC virus antibody (35.5%) and 16 of the 129 patients who tested positive (12.4%) had been treated with natalizumab. Cox regression analysis determined that natalizumab use was the only factor associated with avoiding subsequent surgery (hazard ratio, 0.23; 95% confidence interval, 0.06-0.98). Seroconversion (from testing negative to positive for JC virus antibody) occurred in 1 of the 22 patients (4.5%) who initially tested negative during natalizumab therapy.The prevalence of CD patients exposed to JC virus is comparable with that of the general population. In this retrospective study, prior thiopurine use was associated with an increased risk for testing positive for JC virus antibody. Natalizumab use reduced the risk of subsequent surgery.
View details for DOI 10.1016/j.cgh.2015.05.022
View details for Web of Science ID 000363165700014
View details for PubMedID 26001336
View details for PubMedCentralID PMC4795937
Strictureplasty for Treatment of Crohn's Disease: an ACS-NSQIP Database Analysis
JOURNAL OF GASTROINTESTINAL SURGERY
2015; 19 (5): 905-910
Strictureplasty is an alternative to resection for treatment of Crohn's disease (CD) strictures. It preserves bowel length, and specialized centers report favorable outcomes. Strictureplasty rates, however, are thought to be low, and it was recently removed from required cases for colon and rectal surgery residents. We examined operative characteristics, and trends in its use using a large national database.We examined the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) database from 2005 to 2012, identifying patients with CD who underwent strictureplasty. We identified patient characteristics, outcome variables, and trends in utilization of strictureplasty.A total of 9172 patients underwent surgery for CD. Two hundred fifty-six (2.8 %) underwent strictureplasty. Median preoperative albumin was 3.6. Preoperative steroid use and weight loss rates were 39 and 8 %. Rates of wound infection and organ space infection were 11 and 4 %. Rate of reoperation was 6 %. Outcomes did not change significantly over time (all p = NS). The proportion of CD operations that included a strictureplasty decreased from 5.1 to 1.7 % (OR 0.902 with each additional year, 95 % CI (0.852, 0.960), p < 0.001).Strictureplasty as treatment for CD is decreasing in the ACS-NSQIP database. Infectious complications and reoperation rates following strictureplasty are low and have not changed over time.
View details for DOI 10.1007/s11605-015-2749-8
View details for Web of Science ID 000353198400014
View details for PubMedID 25617078
Initial Surgical Management of Ulcerative Colitis in the Biologic Era
DISEASES OF THE COLON & RECTUM
2014; 57 (12): 1358-1363
The initial minimum operation for ulcerative colitis is a total abdominal colectomy. Healthy patients may undergo proctectomy at the same time; however, for ill patients, proctectomy is delayed. Since the introduction of biologic medications in 2005, ulcerative colitis medical management has changed dramatically.We examined how operative management for ulcerative colitis has changed from the prebiologic to biologic eras.We conducted a retrospective review of data on patients with ulcerative colitis who were included in the Nationwide Inpatient Sample database.This study was conducted at a single university.A total of 1,547,852 patients with ulcerative colitis who were admitted to a US hospital from 1991 to 2011 were included in the study.We examined patients whose initial operation consisted of total abdominal colectomy without proctectomy versus a total proctocolectomy with or without a pouch. We also examined which operation was done at the time of the construction of an ileoanal pouch. Patients who underwent colectomy and pouch construction in the same hospitalization were compared with those who received pouch formation at a subsequent hospitalization.Ulcerative colitis-related admissions rose by 170% during the years examined, and the number of patients who required total abdominal colectomy increased by 44%. Total abdominal colectomy increased by 15%, as opposed to total proctocolectomy (p < 0.001). Pouch construction at a subsequent operation increased by 16% (p = 0.002). Since 2008, total abdominal colectomy has surpassed total proctocolectomy as the most common initial surgical intervention for ulcerative colitis.The Nationwide Inpatient Sample is a retrospective database, and we were limited to examining the variables within it.Total abdominal colectomy is currently the most common initial operation for patients with ulcerative colitis, and an ileoanal pouch is more frequently constructed at a subsequent hospitalization. These trends coincide with the initiation of biologic treatments and may imply that patients are acutely ill at the time of initial operation. Alternately, there may be surgeon-perceived bias of increased surgical risk or a shift in care to specialized surgeons for pouch construction.
View details for DOI 10.1097/DCR.0000000000000236
View details for PubMedID 25380000
- Does Endoscopic Assessment of Mucosal Healing Affect IBD Management? DIGESTIVE DISEASES AND SCIENCES 2014; 59 (10): 2351-2353
Monitoring and management of toxicities in long-term thiopurine therapy.
Gastroenterology & hepatology
2013; 9 (10): 672-674
View details for PubMedID 24764783
Natural history of acute upper GI bleeding due to tumours: short-term success and long-term recurrence with or without endoscopic therapy
ALIMENTARY PHARMACOLOGY & THERAPEUTICS
2013; 38 (2): 144-150
Scant information is available regarding patients with upper gastrointestinal bleeding (UGIB) from tumours.To determine the presentation, endoscopic findings, treatment and outcomes in patients with UGIB from malignant tumours and identify risk factors associated with rebleeding.Consecutive patients who were hospitalised with haematemesis, melena or haematochezia and underwent upper endoscopy were identified retrospectively by reviewing an endoscopy database. Patients with UGIB due to biopsy-proven malignant tumours were studied.Tumours were the source of bleeding in 106 (5%) of 2,166 patients with UGIB. Tumours were oesophageal in 17 (16%), gastric in 77 (73%) and duodenal in 12 (11%). At presentation, 84 (79%) did not have known cancer previously, and 79 (75%) had metastatic disease. Seventy-seven (73%) received transfusions at index hospitalisation. At endoscopy, 32 (30%) had active bleeding (31 oozing, 1 spurting). Among actively bleeding patients, haemostasis was achieved in 12 (86%) of 14 receiving endoscopic therapy and all 18 not receiving endoscopic treatment. Hospitalisation for rebleeding occurred in 50 (49%) of 103 at a median of 30 days (3-885). On multivariate analysis, age ≤60 years (OR = 2.49, 95% CI 1.06-5.81) and haemodynamic instability (OR = 2.42, 95% CI 1.08-5.46) were associated with rebleeding.Patients presenting with tumour-associated UGIB have substantial blood loss, with three-quarters requiring transfusion at presentation. Initial haemostasis occurs in almost all patients, with or without endoscopic therapy, but rebleeding requiring repeat hospitalisation occurs in approximately half the patients and is more common in patients who are ≤60 years of age and have haemodynamic instability at presentation.
View details for DOI 10.1111/apt.12347
View details for Web of Science ID 000320472400007
View details for PubMedID 23710797
Natalizumab in Crohn's Disease: Results From a US Tertiary Inflammatory Bowel Disease Center
INFLAMMATORY BOWEL DISEASES
2013; 19 (3): 621-626
Natalizumab is an efficacious agent for the induction and maintenance of remission in patients with Crohn's disease (CD) who have failed anti-tumor necrosis factor (TNF) agents. We aimed to assess the efficacy and safety of natalizumab outside of clinical trial at a US tertiary center.Retrospective case review of patients with CD receiving natalizumab.Forty-nine patients with CD (28 women; median age, 33 years) receiving natalizumab from April 2008 to November 2011 were identified. Median duration of disease was 180 months (range, 36-576 months); 40 patients had ileocolonic disease, 1 had ileal disease, and 8 had colonic disease. Twenty-one patients had penetrating disease, and 28 had a history of CD-related surgical treatment. Forty-seven patients previously failed treatment with at least 1 anti-TNF agent. Median duration of natalizumab treatment was 7 months (interquartile range, 3-21.5 months). Twenty-four patients (49%) were continuing natalizumab at the time of this review, and 25 discontinued treatment because of the lack of response, side effects, or positive JC virus antibody. Seventeen patients (35%) successfully continued treatment with natalizumab for longer than 12 months, and nonpenetrating disease phenotype was identified as a predictor of longer response (compared with penetrating phenotype; P = 0.013). Nine patients (18.4%) experienced adverse effects, 5 of which were serious, but no case of progressive multifocal leukoencephalopathy occurred.This is the largest series of natalizumab-treated patients with CD. Our results show that natalizumab is an efficacious and safe treatment agent for patients refractory to anti-TNF agents and that nonpenetrating disease phenotype has more durable response over time.
View details for DOI 10.1097/MIB.0b013e31827eea78
View details for Web of Science ID 000316450200035
View details for PubMedID 23429449
View details for PubMedCentralID PMC4779049
Barrett's esophagus in Latinos undergoing endoscopy for gastroesophageal reflux disease symptoms
DISEASES OF THE ESOPHAGUS
2013; 26 (1): 44-49
Previous studies comparing the prevalence of Barrett's esophagus in Latinos and non-Latino whites are inconsistent. The aim of the study is to compare the prevalence of Barrett's esophagus in Latinos and non-Latino whites and to determine risk factors associated with Barrett's esophagus. Between March 2005 and January 2009, consecutive Latino and non-Latino white patients who underwent endoscopy for primary indication for symptoms of gastroesophageal reflux disease were identified by examining the internal endoscopy database at Los Angeles County + USC Medical Center. Barrett's esophagus was defined by columnar-lined distal esophagus on endoscopy confirmed by intestinal metaplasia on histology. Clinical features and endoscopic findings were retrospectively reviewed. The mean age of the 663 patients was 50 ± 12 years, 30% were male, and 92% were Latino. Compared with non-Latino whites, Latinos had more females (72% vs. 46%; P = 0.0001) and more Helicobacter pylori infection (53% vs. 24%; P = 0.003) but less tobacco use (7% vs. 17%; P = 0.01). Overall, 10% (68/663) of all patients had Barrett's esophagus whereas the prevalence was 10% (62/611) among the Latinos and 12% (6/52) among the non-Latino whites (OR 0.9, 95% CI 0.4-2.1; P = 0.75). One patient in the Latino group had high-grade dysplasia. On multivariate analysis, male gender (AOR 2.3, 95% CI 1.4-4.1; P = 0.002), diabetes (AOR 2.2, 95% CI 1.1-4.5; P = 0.03), and age ≥55 years (AOR 2.2, 95% CI 1.3-3.8; P = 0.006) were independently associated with Barrett's esophagus; Latino ethnicity remained nonsignificant (AOR 1.1, 95% CI 0.4-2.7; P = 0.88). In Latinos undergoing endoscopy for gastroesophageal reflux disease symptoms, the prevalence of Barrett's esophagus was 10%, comparable with non-Latino white controls as well as the prevalence previously reported among Caucasians. In addition to established risk factors, diabetes was associated with Barrett's esophagus.
View details for DOI 10.1111/j.1442-2050.2011.01316.x
View details for Web of Science ID 000313251600007
View details for PubMedID 22332868
- Pleural effusion caused by a pancreatic pleural fistula GASTROINTESTINAL ENDOSCOPY 2012; 76 (2): 422-423
- Management of inflammatory bowel disease: past, present and future EXPERT REVIEW OF CLINICAL IMMUNOLOGY 2012; 8 (4): 303-305
Effect of alvimopan and codeine on gastrointestinal transit: A randomized controlled study
CLINICAL GASTROENTEROLOGY AND HEPATOLOGY
2005; 3 (8): 784-791
background & aims: Opiate bowel dysfunction is a significant clinical problem. Our aim was to evaluate the ability of a peripheral mu-opioid antagonist, alvimopan, to reverse the effect of codeine on gastric, small-bowel, and colonic transit time in healthy volunteers.Seventy-four healthy participants (43 women) were randomized in a double-blind, placebo-controlled manner to 1 of 4 groups: alvimopan 12 mg twice daily in the presence and absence of codeine sulfate 30 mg 4 times/day, or codeine or placebo alone. Gastric emptying, small-bowel, and colonic transit were measured by scintigraphy using a 99m-labeled technetium egg meal and 111-labeled indium charcoal delivered to the proximal colon via a delayed-release capsule. The primary end points for colonic transit were geometric center of the colonic counts at 24 hours and time for 50% ascending colon emptying. Analysis of covariance was used to assess the significance of the primary and secondary end points.Codeine delayed gastric, small-bowel, proximal, and overall colonic transit (P < .05). Alvimopan reversed codeine's effect on small bowel and colon (ascending colon and overall colonic transit). Alvimopan also accelerated overall colonic transit compared with placebo. Thus, the mean colonic geometric center at 24 hours was 2.33 with placebo/placebo, 3.25 with alvimopan/placebo (P < .05), 1.5 with placebo/codeine (P < .05), and 2.63 with alvimopan/codeine. Alvimopan did not reverse codeine's delay of gastric emptying.Alvimopan reverses codeine's inhibitory effect on small-bowel and colon transit and has potential for treatment of opiate bowel dysfunction. Alvimopan alone accelerates colonic transit, suggesting that mu-opiate mechanisms participate in the physiologic control of colonic transit.
View details for DOI 10.1053/S1542-3565(05)00434-9
View details for Web of Science ID 000234105700012
View details for PubMedID 16234007