Methylene blue MMX® tablets for chromoendoscopy. Bioavailability, colon staining and safety in healthy volunteers undergoing a full colonoscopy.

Methylene blue-MMX® tablets are proposed as an aid for detection and visualisation of adenomas and carcinomas in patients undergoing colonoscopy, by improving their detection rate and highlighting the presence of the intestinal dysplastic lesions. Single total doses of 100 and 200 mg were administered to healthy volunteers undergoing a bowel cleansing preparation and a full colonoscopy to investigate the colonic staining. The pharmacokinetics of methylene blue and the safety after exposure to the tablets were also investigated. With 200 mg, the best staining, assessed as the sum of acceptable and good staining, was achieved in the ascending colon and rectosigmoid (75% subjects each), the transverse and the descending colon (approximately 63% each). Absence of staining or overstaining were reported for no colonic region of interest in any subject. Similar results were observed in the 100 mg dose group. Methylene blue blood concentrations reached a peak (Cmax) in a median time (Tmax) of 12 h with 100 mg and 16 h with 200 mg. AUC0-t was 10.7 ±â€¯6.7 µg/mLxh after 100 mg and 25.2 ±â€¯7.4 µg/mLxh after 200 mg. Half-life ranged between 9 and 22 h after the lower dose and between 6 and 26 h after the higher dose. The cumulative urinary excretion was about 28% after 100 mg and about 39% after 200 mg up to 60 h post-dose. The overall frequency of adverse events after single dose of the test product administered along with a bowel cleansing preparation was 39%, but only one was related to the test product: abnormal transaminases. The most frequent adverse event was a transient polyuria (17%). One serious adverse event (gastrointestinal haemorrhage) led the subject to study discontinuation and hospitalisation and another subject withdrew the study due to one adverse event (haematemesis). Either event was not related to methylene blue.

Comparison of transanal and external perineal ultrasonography.

Anal endosonography with rotating endoprobes provides state-of-the-art imaging of sphincter integrity; however, the technique is not widely available and requires expensive equipment. Since pelvic anatomy permits the use of standard external ultrasound probes, we tested the feasibility, tolerance and reproducibility of uniplanar perineal sonography, with respect to visualisation of the anal sphincter, using both convex and linear 3.5- to 7.5-MHz and 360 degree rotating 7-MHz probes. Twenty healthy nulliparus female volunteers were investigated. Two operators performed endosonography and perineal sonography in duplicate, each blinded to the findings of the other. We then used this technique to examine 20 postpartum primiparus patients. The examination was well tolerated by all subjects. The internal anal sphincter appeared in perineal sonography as a hypoechogenic ring surrounded by an echogenic ring representing the external anal sphincter. Endosonography revealed six sphincter tears, four external and internal sphincter tears, one isolated external tear and one isolated internal tear. Perineal sonography recognised in all cases external sphincter tears. In one case the internal sphincter defect was missed. Perineal sonography appears to be a feasible alternative to anal endosonography in female patients and provides good information on external sphincter defects suggesting that this procedure might be particularly useful in incontinence screening. Perineal sonography gives a good image of internal sphincter. The lack of an isolated internal defect cannot be considered as relevant to our study.