-
1.
Effect of the Wetting Agent Sodium Lauryl Sulfate on the Pharmacokinetics of Alectinib: Results From a Bioequivalence Study in Healthy Subjects.
Morcos, PN, Parrott, N, Banken, L, Timpe, C, Lindenberg, M, Guerini, E, Dall, G, Bogman, K, Sturm, C, Zeaiter, A, et al
Clinical pharmacology in drug development. 2017;(3):266-279
Abstract
The anaplastic lymphoma kinase (ALK) inhibitor alectinib is an effective treatment for ALK-positive non-small-cell lung cancer. This bioequivalence study evaluated the in vivo performance of test 3 formulations with the reduced wetting agent sodium lauryl sulfate (SLS) content. This randomized, 4-period, 4-sequence, crossover study compared alectinib (600 mg) as 25%, 12.5%, and 3% SLS hard capsule formulations with the reference 50% SLS clinical formulation in healthy subjects under fasted conditions (n = 49), and following a high-fat meal (n = 48). Geometric mean ratios and 90% confidence intervals (CIs) for Cmax , AUC0-last , and AUC0-∞ of alectinib, its major active metabolite, M4, and alectinib plus M4 were determined for the test formulations versus the reference formulation. Bioequivalence was concluded if the 90%CIs were within the 80% to 125% boundaries. The 25% SLS formulation demonstrated bioequivalence to the reference 50% SLS formulation for Cmax , AUC0-last , and AUC0-∞ of alectinib, M4, and alectinib plus M4 under both fasted and fed conditions. Further reductions in SLS content (12.5% and 3% SLS) did not meet the bioequivalence criteria. Cross-group comparisons showed an approximately 3-fold positive food effect. Reducing SLS to 25% resulted in a formulation that is bioequivalent to the current 50% SLS formulation used in alectinib pivotal trials.
-
2.
Lactulose vs polyethylene glycol 3350--electrolyte solution for treatment of overt hepatic encephalopathy: the HELP randomized clinical trial.
Rahimi, RS, Singal, AG, Cuthbert, JA, Rockey, DC
JAMA internal medicine. 2014;(11):1727-33
-
-
Free full text
-
Abstract
IMPORTANCE Hepatic encephalopathy (HE) is a common cause of hospitalization in patients with cirrhosis. Pharmacologic treatment for acute (overt) HE has remained the same for decades. OBJECTIVE To compare polyethylene glycol 3350-electrolyte solution (PEG) and lactulose treatments in patients with cirrhosis admitted to the hospital for HE. We hypothesized that rapid catharsis of the gut using PEG may resolve HE more effectively than lactulose. DESIGN, SETTING, AND PARTICIPANTS The HELP (Hepatic Encephalopathy: Lactulose vs Polyethylene Glycol 3350-Electrolyte Solution) study is a randomized clinical trial in an academic tertiary hospital of 50 patients with cirrhosis (of 186 screened) admitted for HE. INTERVENTIONS Participants were block randomized to receive treatment with PEG, 4-L dose (n = 25), or standard-of-care lactulose (n = 25) during hospitalization. MAIN OUTCOMES AND MEASURES The primary end point was an improvement of 1 or more in HE grade at 24 hours, determined using the hepatic encephalopathy scoring algorithm (HESA), ranging from 0 (normal clinical and neuropsychological assessments) to 4 (coma). Secondary outcomes included time to HE resolution and overall length of stay. RESULTS A total of 25 patients were randomized to each treatment arm. Baseline clinical features at admission were similar in the groups. Thirteen of 25 patients in the standard therapy arm (52%) had an improvement of 1 or more in HESA score, thus meeting the primary outcome measure, compared with 21 of 23 evaluated patients receiving PEG (91%) (P < .01); 1 patient was discharged before final analysis and 1 refused participation. The mean (SD) HESA score at 24 hours for patients receiving standard therapy changed from 2.3 (0.9) to 1.6 (0.9) compared with a change from 2.3 (0.9) to 0.9 (1.0) for the PEG-treated groups (P = .002). The median time for HE resolution was 2 days for standard therapy and 1 day for PEG (P = .01). Adverse events were uncommon, and none was definitely study related. CONCLUSIONS AND RELEVANCE PEG led to more rapid HE resolution than standard therapy, suggesting that PEG may be superior to standard lactulose therapy in patients with cirrhosis hospitalized for acute HE. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT01283152.
-
3.
Randomised clinical trial: macrogol/PEG 3350+electrolytes versus prucalopride in the treatment of chronic constipation -- a comparison in a controlled environment.
Cinca, R, Chera, D, Gruss, HJ, Halphen, M
Alimentary pharmacology & therapeutics. 2013;(9):876-86
-
-
Free full text
-
Abstract
BACKGROUND Constipation is a common condition for which PEG 3350 is an established treatment and prucalopride has recently been approved for this indication. AIM: To compare the efficacy, safety and impact on quality of life (QoL) of PEG 3350 plus electrolytes (PEG 3350+E) vs. prucalopride in females with chronic constipation (CC) in whom laxatives have previously failed to provide adequate relief. METHODS In this single-centre, randomised, double-blind, double-dummy study, patients with CC [<3 spontaneous complete bowel movements (SCBM)/week] remained in a controlled environment and received either a 26 g split dose of PEG 3350+E (N = 120) or 1-2 mg prucalopride (N = 120) daily for 28 days following a 14-day run-in period. The primary endpoint was the proportion of patients having ≥3 SCBMs during the last treatment week. RESULTS Non-inferiority of PEG 3350+E to prucalopride was demonstrated in the per-protocol population [difference, 10.1% (66.67% vs. 56.52%), 97.5% lower confidence interval (CI) -2.7%, above the preset margin of -20%] and approached superiority in the modified intent-to-treat population (difference, 9.8%, 97.5% lower CI, -3.1%). Statistically significant differences in favour of PEG 3350+E were observed for most secondary variables (bowel movements, stool weight, consistency, time to next SCBM, patient perception of straining and completeness of defecation). Colonic transit time was dramatically reduced in both arms. Both treatments were well tolerated. CONCLUSION PEG 3350+E was at least as effective as and generally better tolerated than prucalopride as a treatment for chronic constipation in this study population (NCT01251822; http://www.clinicaltrials.gov).
-
4.
Achieving quality in colonoscopy: bowel preparation timing and colon cleanliness.
Athreya, PJ, Owen, GN, Wong, SW, Douglas, PR, Newstead, GL
ANZ journal of surgery. 2011;(4):261-5
Abstract
BACKGROUND Colonoscopy is considered the gold standard for investigation of large bowel pathology. Numerous factors influence the efficacy of bowel preparation for colonoscopy. Inadequate bowel preparation can lead to missed pathology. Timing of fasting and bowel preparation, timing of procedure and possibly patient bowel habit and presence of diverticula may have an influence on the quality of the preparation. The aim of this study was to investigate the quality of cleansing of sodium picosulfate (Picoprep-3™, Pharmatel Fresenius Kabi Pty Ltd, Pymble, NSW, Australia) with different administration schedules and to evaluate whether patient's bowel patterns influence the quality of cleansing. METHODS Three hundred twenty-five patients (175 morning and 150 afternoon procedures) were interviewed prior to colonoscopy to evaluate bowel habit and timing of preparation administration. Quality of cleansing was then assessed during colonoscopy using a 5-point scale. Further factors analysed included the patient's prior bowel habit and the presence of diverticula at colonoscopy. Procedural end points evaluated included procedure total time, caecal intubation time and withdrawal times. RESULTS The quality of cleansing for individual bowel segments was worse for afternoon procedures (P < 0.05 for some segments) and for patients with prior constipation (P < 0.05 for descending colon segments). Caecal intubation times were shorter for patients with diarrhoea and longer for female patients, who also had shorter withdrawal times. No correlation was found between the procedural end points (total duration, caecal intubation time and withdrawal times) and the timing of fasting. CONCLUSIONS Quality of cleansing is significantly improved when bowel preparation is taken entirely the day prior to colonoscopy. Patients with prior constipation demonstrated poorer cleansing.
-
5.
Anti-inflammatory effect of pimecrolimus in the sodium lauryl sulphate test.
Engel, K, Reuter, J, Seiler, C, Schulte Mönting, J, Jakob, T, Schempp, CM
Journal of the European Academy of Dermatology and Venereology : JEADV. 2008;(4):447-50
Abstract
BACKGROUND Pimecrolimus is a calcineurin inhibitor used for the topical treatment of inflammatory skin diseases. We have shown previously that pimecrolimus cream is not effective on intact skin in the ultraviolet erythema test. OBJECTIVE To test the anti-inflammatory effect of pimecrolimus cream after damage of the skin barrier by sodium lauryl sulphate (SLS) in a randomised, placebo-controlled, observer-blinded study. METHODS SLS (3% v/v) was applied under occlusion on the back of 36 healthy volunteers for 24 h. Subsequently, the test areas were treated for 24 h with pimecrolimus cream, 1% hydrocortisone in a hydrophilic ointment, and the vehicle alone over three consecutive days. One control area remained untreated. The erythema index and the transepidermal water loss (TEWL) served as readout parameters to assess the SLS-induced skin irritation. RESULTS Pimecrolimus cream and 1% hydrocortisone cream significantly reduced the SLS-induced erythema. The two test preparations did not have a significant effect on the TEWL. CONCLUSION After damage to the skin barrier by SLS, pimecrolimus seems to penetrate into the skin as shown by a reduction of the irritation-induced erythma. These data further support the notion that pimecrolimus is selectively effective in the treatment of skin disorders with an impaired function of the epidermal barrier.
-
6.
Effects of sodium lauryl sulphate (SLS), present in dentifrice, on volatile sulphur compound (VSC) formation in morning bad breath.
Peruzzo, DC, Salvador, SL, Sallum, AW, da Nogueira-Filho, GR
Journal of the International Academy of Periodontology. 2008;(4):130-6
Abstract
The purpose of the present investigation was to evaluate the effects of sodium lauryl sulphate (SLS), present in a commercial dentifrice, on the formation of volatile sulphur compounds (VSC) and tongue coating in a panel of periodontally healthy subjects. A two-step blinded, crossover, randomized study was carried out in 25 dental students with healthy periodontium; these were divided into two experimental groups: SLS (dentifrice with SLS) and WSLS (dentifrice without SLS). The volunteers received the designated dentifrice and a new toothbrush for a 3x/day brushing regimen for 2 periods of 30 days. A seven-day washout interval was used between the periods. The assessed parameters were: plaque index (PI), gingival index (GI), organoleptic breath (ORG), VSC levels by portable sulphide monitor before (H1) and after (H2) cleaning of the tongue, tongue coating wet weight (TC) and benzoyl-DL-arginine-naphthylamide (BANA) test from tongue coating samples. The intra-group analysis showed a decrease in the median of organoleptic scores from 3 to 2 after 30 days for the SLS group (p < 0.05). The inter-group analysis showed lower values in ORG and H1 for the SLS group (p < 0.05). There was no difference between the amount of TC in SLS and WSLS groups. In the BANA test, the presence of SLS did not affect the BANA number of +/- results (p > 0.05). These findings suggest that sodium lauryl sulphate (SLS), present in dentifrice, appears to prevent VSC formation in morning bad breath regardless of the amount of tongue coating in periodontally healthy subjects.
-
7.
Quality and effect of single dose versus split dose of polyethylene glycol bowel preparation for early-morning colonoscopy.
Park, JS, Sohn, CI, Hwang, SJ, Choi, HS, Park, JH, Kim, HJ, Park, DI, Cho, YK, Jeon, WK, Kim, BI
Endoscopy. 2007;(7):616-9
Abstract
BACKGROUND AND STUDY AIMS The conventional procedure of ingestion of an entire dose of polyethylene glycol solution on the day before early-morning colonoscopy may result in poor bowel preparation. The aim of this study was to evaluate the efficacy and effect of a split-dose ingestion of polyethylene glycol for early-morning colonoscopy. METHODS A total of 303 age- and sex-matched consecutive individuals presenting for medical check-ups were randomly assigned to receive either 4 L of polyethylene glycol solution with a soft diet on the day before colonoscopy (n = 152; group A), or 3 L of polyethylene glycol solution with a soft diet on the preceding day and then 1 L of the solution on the day of colonoscopy (n = 151; group B). The quality of bowel preparation was evaluated using the Ottawa scale, and the time to cecal intubation and the technical difficulty during the procedure were also recorded. RESULTS There was no difference in compliance between group A (single-dose) and group B (split-dose). The quality of bowel preparation was better in group B compared with group A. When the participants were categorized according to compliance (good compliance, 116 in group A, 119 in group B; poor compliance, 36 in group A, 32 in group B), the quality of the bowel preparation had a higher score in the good compliance compared with the poor compliance group, and in group B this difference was usually significant. CONCLUSIONS Split-dose bowel preparation with polyethylene glycol solution provided a better quality preparation than the conventional method for patients undergoing early-morning colonoscopy.
-
8.
A randomized, multicenter study comparing the safety and efficacy of sodium phosphate tablets with 2L polyethylene glycol solution plus bisacodyl tablets for colon cleansing.
Johanson, JF, Popp, JW, Cohen, LB, Lottes, SR, Forbes, WP, Walker, K, Carter, E, Zhang, B, Rose, M
The American journal of gastroenterology. 2007;(10):2238-46
Abstract
OBJECTIVE The safety and efficacy of NaP tablets have not been compared with 2L PEG lavage solution. A multicenter, investigator-blinded study was conducted to compare the colon-cleansing efficacy of a new NaP tablet formulation with that of 2L PEG solution plus bisacodyl tablets in adults undergoing colonoscopy. METHODS A total of 481 patients were randomized to receive either 32 tablets (48 g) of NaP or 2L PEG solution plus 4 (20 mg) bisacodyl tablets. Quality of colon cleansing was assessed using a 4-point scale (1 = excellent, 2 = good, 3 = fair, and 4 = inadequate), and the primary efficacy end point was mean overall colon-cleansing score. Safety assessments included recording of adverse events and changes in biochemical tests and vital signs. RESULTS A total of 411 patients were included in the efficacy analysis. The mean overall and ascending colon-cleansing scores for NaP tablets were significantly better than PEG plus bisacodyl (overall 1.5 vs 1.8, ascending 1.4 vs 1.8, P < 0.0001 for both). Patients treated with NaP tablets experienced significantly fewer adverse events (66%vs 82%, P= 0.0003) and gastrointestinal symptoms (64%vs 79%, P= 0.0001) compared with patients receiving PEG plus bisacodyl. Patients receiving NaP tablets were significantly less likely to experience abdominal distention, abdominal pain, and vomiting than patients receiving PEG plus bisacodyl (P < 0.0012). Transient fluctuations in laboratory parameters were observed in both treatment groups; however, the fluctuations were more common and of greater magnitude in the NaP group particularly in phosphorous, sodium, and potassium. CONCLUSION The colon-cleansing efficacy of the new 32-tablet NaP dosing regimen in this study was found to be significantly better than the 2L PEG solution plus bisacodyl tablets regimen. The 32-tablet NaP dosing regimen was associated with fewer adverse events. As expected electrolyte shifts were more common and of greater magnitude in the NaP group compared with the PEG plus bisacodyl group; however, both treatment groups demonstrated significant changes in electrolytes and creatinine.
-
9.
Macrogol for the treatment of constipation in Parkinson's disease. A randomized placebo-controlled study.
Zangaglia, R, Martignoni, E, Glorioso, M, Ossola, M, Riboldazzi, G, Calandrella, D, Brunetti, G, Pacchetti, C
Movement disorders : official journal of the Movement Disorder Society. 2007;(9):1239-44
Abstract
Chronic constipation is the most frequent symptom of autonomic system involvement in Parkinson's disease (PD). Quite often the symptom is severe and impairs patients' quality of life. The objective of this study is to determine the efficacy and safety of an isosmotic macrogol solution for the treatment of constipation in PD patients, in a double-blind, placebo-controlled study. A total of 57 PD patients with constipation were randomly assigned to receive an isosmotic macrogol electrolyte solution (MC-ES; 29 patients) or placebo (28 patients) for 8 weeks. Treatment efficacy was defined as complete relief of the symptom or a marked improvement of two of the following indicators: stool frequency, straining, stool consistency, use of rectal laxatives as a rescue therapy. The responder rates were significantly higher in the MC-ES group both at the first (4 weeks; P < 0.0003) and at the final evaluation (8 weeks; P < 0.0012). The frequency of bowel movements (P < 0.002) and stool consistency (P < 0.006) were significantly changed in the MC-ES group compared to the placebo group. At the final evaluation, a rectal laxative was used by 2 (12.5%) patients on placebo, whereas no use was recorded in the MC-ES group. Responder rate for straining showed a favorable trend in patients treated with macrogol versus placebo. Unified Parkinson's Disease Rating Scale Part III and Parkinson's Disease Questionnaire (PDQ-39) did not show any significant modification in either group during the 8-week treatment period. The results of this placebo-controlled study show the efficacy of MC-ES in the treatment of constipation in PD. MC-ES was well-tolerated and did not affect the course of PD.
-
10.
The impact of colon preparation timing on colonoscopic detection of colorectal neoplasms--a prospective endoscopist-blinded randomized trial.
Chiu, HM, Lin, JT, Wang, HP, Lee, YC, Wu, MS
The American journal of gastroenterology. 2006;(12):2719-25
Abstract
OBJECTIVES Timing of colon preparation might influence the cleansing condition of the colon and therefore affect the quality and diagnostic yield of colonoscopy. This study compared two different timings of colon preparation to assess the efficacy of colon cleansing and diagnostic yield of colorectal neoplasms during colonoscopy. METHODS One hundred twenty-one eligible subjects who had colorectal neoplasms detected at a screening colonoscopy were randomly assigned to receive colon preparation with polyethylene glycol electrolyte lavage solution (PEG-ELS) either on the day of (on the day group) or the night before (previous night group) a second colonoscopy. The condition of colon preparation and the diagnostic yield of colorectal neoplasms were recorded and compared between the two groups for the initial and second colonoscopies. RESULTS Fifty-nine subjects received colon preparation on the night before and 60 subjects received colon preparation the day of a second colonoscopy. Colon preparation for the second colonoscopy was better in the on-the-day group than in the previous night group (P= 0.003). Colon preparation for the second colonoscopy was better for each group in comparison with the initial colonoscopy (P < 0.0001). An interobserver variability analysis using 20 randomly selected colonoscopies from the two groups revealed good correlation among four colonoscopists. More lesions were detected in group A during the second colonoscopy (P= 0.028). CONCLUSION Colon preparation on the day of colonoscopy has a better cleansing quality and higher diagnostic yield. Subjects who had lesions detected during the initial screening colonoscopy had better colon cleansing for the second colonoscopy regardless of the timing of preparation.