Methylene blue MMX® tablets for chromoendoscopy. Safety tolerability and bioavailability in healthy volunteers

• Published in: Contemporary clinical trials 2012-03, Vol.33 (2), p.260-267
• Main Authors: Repici, A, Di Stefano, A.F.D, Radicioni, M.M, Jas, V, Moro, L, Danese, S
• Format: Article
• Language: English
• Subjects: Administration, Oral; Adult; Biological Availability; Cardiovascular; Chromoendoscopy; Colonoscopy - methods; Cross-Over Studies; Dose-Response Relationship, Drug; Drug Tolerance; Enzyme Inhibitors - administration & dosage; Enzyme Inhibitors - pharmacokinetics; Female; Follow-Up Studies; Healthy subjects; Hematology, Oncology and Palliative Medicine; Humans; Intestinal Mucosa - drug effects; Intestinal Mucosa - metabolism; Male; Methylene blue; Methylene Blue - administration & dosage; Methylene Blue - pharmacokinetics; Middle Aged; MMX; Pharmacokinetics; Reference Values; Retrospective Studies; Tablets; Young Adult
• ISSN: 1551-7144; 1559-2030
• DOI: 10.1016/j.cct.2011.11.006

Abstract Methylene blue-MMX® tablets are proposed as colonic diagnostic staining. Methylene blue taken prior to colonoscopy is expected to provide an effective staining of colonic and rectal mucosa leaving unstained the dysplastic or polypoid areas. The present single dose, open-label study investigated the safety of methylene blue after single oral doses of 200 and 400 mg in healthy volunteers. The absolute bioavailability was also investigated after the intake of 2 L of bowel cleansing preparation in 2 h and by comparing the dose of 200 mg with a single iv dose of 100 mg in the same subjects. Only non-serious adverse events occurred. Related events occurred to 8/22 subjects. Most of the events were mild and transient. Abnormal transaminases, gastrointestinal disorders and dysuria frequency were 13.6%. After intake of the laxative and the oral dose of 200 mg, systemic exposure to methylene blue was shown in all subjects with concentrations increasing for 12 h. The peak was reached in a median of 16 h. Peak blood concentration did not increase proportionally with the dose. AUC 0–t was 32.94 μg/mL × h after 200 mg and 38.08 μg/mL × h after 400 mg. Half life ranged between 14 and 27 h after the lower dose and between 6 and 26 h after the higher dose. The cumulative excretion was about 40% of the injected dose, 39.67% after 200 mg and 23.48% after 400 mg. Absolute bioavailability of methylene blue calculated as ratio between AUC0–t oral/iv corrected for the dose was on average Fabs = 139.19 ± 52.00%.