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PubMed2005

The influence of the sennosides on absorption of glycyrrhetic acid in rats.

In the course of our clinical studies of Kampo medicine (traditional Japanese medicines), we observed the pharmacokinetic interactions between two herbs. When Onpito (TJ-8117, Kampo medicine) containing licorice and rhubarb was administered orally to human subjects, we observed that the AUC(0-lim) and Cmax of glycyrrhetic acid (GA) in plasma were lower than those treated with other Kampo medicines containing licorice. In this study, we demonstrate the pharmacokinetic interactions of GA derived from glycyrrhizinic acid (GL) in licorice and anthraquinones derived from rhubarb. To our knowledge, this is the first report to investigate the pharmacokinetic interactions between two herbs. When GL was orally co-administrated to rats with a non-effective dose of sennoside A having purgative activity, the AUC(0-lim) and Cmax of GA decreased. In addition, sennoside A did not affect the metabolism of GL by the intestinal bacteria in vitro. In the examination using an in situ loop of rat colon, the remaining ratio of GA rose drastically by the co-administration of sennoside A, sennidin A and rhein. Observed inhibition activity of these anthraquinones on GA absorption depended on the concentration of the components added. The maximum inhibition ratio was approximately 75% by rhein, 60% by sennoside A and 25% by sennidin A. We conclude that the decrease of the pharmacokinetic parameters of GA in human plasma observed in the clinical study of TJ-8117 is attributable to an interactive action of absorption from the intestinal tract by anthraquinones contained in or derived from rhubarb.

Animals↗
PubMed1985

Enzymatic reduction of sennidin and sennoside in Peptostreptococcus intermedius.

Peptostreptococcus intermedius, one of the dominant bacteria of human intestine, reduced sennidin and sennoside to rheinanthrone and 8-glucosyl-rheinanthrone, respectively, and these reduction rates were stimulated by the addition of nicotinamide adenine dinucleotide (reduced form) (NADH), flavin adenine dinucleotide (FAD) and glucose. The reduction was accelerated by removing oxygen from the incubation tubes, which indicates the inhibition of the reduction by O2. Thus, for the maximal activity, the reaction system required an anaerobic condition and cofactors, NADH and FAD. This bacterium also reduced methyl orange, whose mode of reduction resembled that of sennidin reduction. More than 80% of these activities were recovered in the supernatant fraction after sonication of the bacterial suspension, and these activities were purified together by means of Sephadex G-200 gel-filtration and diethylaminoethyl-cellulose column chromatography. The purified enzyme reduced FAD and benzyl viologen in the presence of NADH under an anaerobic condition.

Anthracenes↗
PubMed1992

[Determination of sennoside A in oriental pharmaceutical decoctions containing Rhei Rhizoma by ion-pair high-performance liquid chromatography].

A simple method using ion-pair high-performance liquid chromatography was established for the rapid and precise determination of sennoside A in oriental pharmaceutical decoctions containing Rhei Rhizoma. This method was compared with other two methods, i.e. ion-suppression and phosphate buffer methods. Sennoside A was eluted without interference in this ion-pair method, while the determination of sennoside A was interfered by co-existing components in the other two methods.

Anthraquinones↗
PubMed1999

[Determination of sennoside A and sennoside B in formulation using capillary electrophoresis].

The determination of sennoside A (SA) and sennoside B (SB) by capillary zone electrophoresis was developed. The separation of SA and SB was performed in 100 mM of the 3-[cyclohexylamino]-1-propanesulfonic acid (CAPS) buffer (pH 10.0), and the migration time of SA and SB was found to be both less than 7 min. This method was applied to the analyses of seven commercial formulations containing SA and SB without previous treatment. The statistical comparison of the results obtained from both capillary electrophoresis and HPLC methods revealed an absolute correlation.

Anthraquinones↗
PubMed2000

Calcium polycarbophil, a water absorbing polymer, increases bowel movement and prevents sennoside-induced diarrhea in dogs.

The effects of calcium polycarbophil (CP), a water-absorbing polymer, on bowel movement were examined in comparison with known laxatives and anti-diarrheal agents in dogs, a species that resembles humans for stool output. CP increased stool frequency, fecal water content and fecal weight in a dose-dependent manner, but did not induce diarrhea. Sennoside and carboxymethylcellulose sodium (CMC-Na) increased fecal water content and induced diarrhea at lower doses than that which enhanced stool frequency. Trimebutine decreased stool frequency, fecal weight and fecal water content, resulting in inhibition rather than stimulation of defecation. In sennoside-induced diarrhea, loperamide and CP improved stool consistency and this was accompanied by reduced fecal moisture and frequency of diarrhea. In contrast, CMC-Na aggravated stool consistency with increased fecal water content and frequency of diarrhea, and trimebutine had little noticeable effect apart from reducing fecal weight. Our results show that CP has both laxative and anti-diarrheal effects in dogs and differed from conventional laxatives and anti-diarrheal agents. CP may be a suitable agent for treatment of idiopathic constipation, secretory diarrhea and irritable bowel syndrome with alternating constipation and diarrhea and with either predominating in terms of less side effects such as diarrhea or constipation.

Acrylic Resins↗
PubMed2003

Skin breakdown and blisters from senna-containing laxatives in young children.

BACKGROUND: At the direction of the Food and Drug Administration, phenolphthalein was removed from all over-the-counter laxatives in 1999. Phenolphthalein was then replaced in most laxative products with the natural product senna from Cassia acutifolia Delile, which contains various anthraquinones. No data are available on the safety of senna use in children <6 years of age. OBJECTIVE: To describe the clinical outcomes of exposure to unintentional ingestion of senna-containing laxatives in young children. METHODS: All ingestion exposures of senna-containing laxatives in children <5 years of age from 6 poison centers over a 9-month period were evaluated. Inclusion criteria required 24-hour follow-up and the presence of diarrhea to confirm ingestion. Parents were told routinely that severe diaper rash was possible and to protect the perianal area with frequent cleansing and a barrier ointment if the child was wearing diapers. RESULTS: During the study period, 111 cases were reported: 19 children experienced no diarrhea, 4 were lost to follow-up, and 88 exposures were evaluated. Fifty-two children (59%) were </=2 years old. Fifty children remained in diapers, 28 children were fully toilet trained, and 10 wore diapers (pull-up pants) overnight. Twenty-nine children (33%) experienced severe diaper rash. The mean +/- SD time to recognition of the diaper rash was 15.6 +/- 8.6 hours. Ten children (11%) had blisters and skin sloughing. There was a significant increase in severe diaper rash (p < 0.05) and onset of blisters and skin breakdown (p < 0.05) in children wearing diapers versus those who were fully toilet trained. The mean time to onset of blisters was 14.5 +/- 6.8 hours. Skin burns and loss were seen primarily on the buttocks and perineum, loosely following the diaper area. CONCLUSIONS: Unintentional ingestion of senna-containing laxatives in young children may potentially cause severe diaper rash, blisters, and skin sloughing.

Blister↗
PubMed2006

Factitious diarrhea induced by stimulant laxatives: accuracy of diagnosis by a clinical reference laboratory using thin layer chromatography.

BACKGROUND: Surreptitious ingestion of laxatives can lead to serious factitious diseases that are difficult to diagnose. Most cases involve ingestion of bisacodyl or senna. Thin layer chromatography (TLC) of urine or stool is the only commercially available test for these laxatives. Such testing is considered highly reliable, but its accuracy in clinical practice is unknown. Our aim was to evaluate the reliability of TLC laxative testing by a clinical reference laboratory in the United States. METHODS: Diarrhea was induced in healthy volunteers by ingestion of bisacodyl, senna, or a control laxative (n = 11 for each laxative group). Samples of urine and diarrheal stool were sent in blinded fashion to the clinical reference laboratory for bisacodyl and senna analysis. RESULTS: TLC testing for bisacodyl-induced diarrhea revealed a sensitivity of 73% and specificity of 91% when urine was tested and sensitivity and specificity of 91% and 96%, respectively, when stool was analyzed. When diarrhea was induced by senna, the TLC assay for senna failed to identify even a single urine or stool specimen as positive (zero% sensitivity). CONCLUSIONS: Considering the expected prevalence of surreptitious laxative abuse in patients with chronic idiopathic diarrhea (2.4%-25%, depending on the clinical setting), TLC of urine or stool for bisacodyl by this reference laboratory would often produce misleading results, and testing for senna would have no clinical value. The major problems are false-positive tests for bisacodyl and false-negative tests for senna.

Bisacodyl↗
PubMed2006

Pharmacologic management of constipation in the critically ill patient.

STUDY OBJECTIVE: To compare the effectiveness of common laxatives in producing a bowel movement in patients admitted to a medical intensive care unit (MICU). DESIGN: Retrospective medical record review. SETTING: MICU of an academic medical center. PATIENTS: Ninety-five patients admitted to the MICU from July 1-October 31, 2004. MEASUREMENTS AND MAIN RESULTS: Fifty patients satisfied the inclusion criteria. Patient-specific data such as age, weight, sex, length of MICU stay, Acute Physiology and Chronic Health Evaluation (APACHE) II score, dietary intake, opioid intake, laxative intake, and bowel movements were recorded during the first 96 hours of admission. Logistic regression analysis was used to compare patients who did and did not have a bowel movement. Of the 50 patients, 25 did not have a bowel movement during the first 96 hours of MICU admission. Patients given a stimulant laxative (senna, bisacodyl) and/or an osmotic laxative (lactulose, milk of magnesia) were more likely to have a bowel movement (odds ratio [OR] 26.6, 95% confidence interval [CI] 3.2-221, p=0.002). Opioid intake, expressed as logarithmic morphine equivalents, was negatively associated with occurrence of a bowel movement (OR 0.76, 95% CI 0.59-0.97, p=0.027). Disease severity, as determined by APACHE II score, was also negatively associated with a bowel movement (OR 0.84, 95% CI 0.7-0.99, p=0.04). CONCLUSION: Critically ill patients have a high frequency of constipation, and opioid therapy is a significant risk factor. Routine administration of stimulant or osmotic laxatives should be considered for this patient population.

Analgesics, Opioid↗
PubMed1997

Stool form scale as a useful guide to intestinal transit time.

BACKGROUND: Stool form scales are a simple method of assessing intestinal transit rate but are not widely used in clinical practice or research, possibly because of the lack of evidence that they are responsive to changes in transit time. We set out to assess the responsiveness of the Bristol stool form scale to change in transit time. METHODS: Sixty-six volunteers had their whole-gut transit time (WGTT) measured with radiopaque marker pellets and their stools weighed, and they kept a diary of their stool form on a 7-point scale and of their defecatory frequency. WGTT was then altered with senna and loperamide, and the measurements were repeated. RESULTS: The base-line WGTT measurements correlated with defecatory frequency (r = 0.35, P = 0.005) and with stool output (r = -0.41, P = 0.001) but best with stool form (r = -0.54, P < 0.001). When the volunteers took senna (n = 44), the WGTT decreased, whereas defecatory frequency, stool form score, and stool output increased (all, P < 0.001). With loperamide (n = 43) all measurements changed in the opposite direction. Change in WGTT from base line correlated with change in defecatory frequency (r = 0.41, P < 0.001) and with change in stool output (n = -0.54, P < 0.001) but best with change in stool form (r = -0.65, P < 0.001). CONCLUSIONS: This study has shown that a stool form scale can be used to monitor change in intestinal function. Such scales have utility in both clinical practice and research.

Adult↗
PubMed2006

Comparative study of two bowel preparation regimens for colonoscopy: senna tablets vs sodium phosphate solution.

AIM: To compare the efficacy and acceptance of senna tablet and sodium phosphate solution for bowel preparation before colonoscopy. METHODS: One hundred and thirty four patients, who needed elective colonoscopy, were randomly allocated to take 180 mg senna tablet or 95 mL sodium phosphate solution on the day before colonoscopy. The efficacies of both laxatives were compared using the mean difference of colon-cleanliness score of the rectum, sigmoid segments, descending colon, transverse colon and cecum. The scores were rated by two observers who were blinded to the laxatives administered. The higher score means that the colon is cleaner. The efficacy of both laxatives were equivalent if the 95% confidence interval of the mean difference of the score of colon lie within -1 to +1. RESULTS: On intention-to-treat analysis, the mean cleanliness scores in the four segments of colon except the cecum were higher in the sodium phosphate group than those in senna group (7.9 +/- 1.7 vs 8.3 +/- 1.5, 8.0 +/- 1.8 vs 8.5 +/- 1.4, 7.9 +/- 2.0 vs 8.5 +/- 1.3, 7.9 +/- 2.0 vs 8.2 +/- 1.4 and 7.2 +/- 1.7 vs 6.9 +/- 1.4, respectively). The 95% confidence intervals (95% CI) of mean difference in each segment of colon were not found to lie within 1 point which indicated that their efficacies were not equivalent. The taste of senna was better than sodium phosphate solution. Also, senna had fewer side effects. CONCLUSION: The efficacy of senna is not equivalent to sodium phosphate solution in bowel preparation for colonoscopy, but senna may be considered an alternative laxative.

Adult↗