title: Effect of food on the pharmacokinetics of oral MMI270B (CGS 27023A), a novel matrix metalloproteinase inhibitor.
abstract: MMI270B is a matrix metalloproteinase inhibitor (MMPI) with in vitro and in vivo activity. To exert optimal target inhibition, MMPI must be given chronically, and therefore, oral bioavailability is important. We analyzed the effect of food intake on AUC0-8 h, Cmax, and Tmax. Seventeen patients were entered into the study. Doses of MMI270B were 150, 400, and 600 mg. The first day, patients ingested the drug in a fasted state and were not allowed to eat for 2 h. The second day, patients ingested the drug 30 min after a light breakfast. Mean AUC0-8 h was not significantly influenced by food intake. Plasma concentrations were well above the IC50 of several MMPs at all doses tested. Mean Cmax was significantly decreased after food intake. Mean Tmax was significantly delayed after food intake. Food intake did not result in a significant change in exposure to MMI270B (AUC0-8 h) but did result in a significant, although not clinically relevant, decrease in peak plasma levels and time to reach peak plasma levels. No specific guidelines concerning the ingestion of MMI270B in either a fed or a fasted state are recommended.
authors.affiliation: Department of Medical Oncology, Rotterdam Cancer Institute (Daniel den Hoed Kliniek), The Netherlands. eskens@oncd.azr.nl
authors.forename: F A
authors.initials: FA
authors.lastname: Eskens
authors.forename: N C
authors.initials: NC
authors.lastname: Levitt
authors.forename: A
authors.initials: A
authors.lastname: Sparreboom
authors.forename: L
authors.initials: L
authors.lastname: Choi
authors.forename: R
authors.initials: R
authors.lastname: Mather
authors.forename: J
authors.initials: J
authors.lastname: Verweij
authors.forename: A L
authors.initials: AL
authors.lastname: Harris
mesh_terms: D000284:Administration, Oral; D019540:Area Under Curve; D004305:Dose-Response Relationship, Drug; D004435:Eating; D005215:Fasting; D006801:Humans; D006877:Hydroxamic Acids; D008666:Metalloendopeptidases / Q000037:antagonists & inhibitors*; D009369:Neoplasms / Q000097:blood / Q000188:drug therapy*; D019518:Postprandial Period; D011480:Protease Inhibitors / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics*; D011719:Pyrazines; D013449:Sulfonamides
chemical_list: C097658:CGS 27023A; D006877:Hydroxamic Acids; D011480:Protease Inhibitors; D011719:Pyrazines; D013449:Sulfonamides; D008666:Metalloendopeptidases