Osmotic dehydration: More than water loss and solid gain.

The immersion of food in a hypertonic solution results in an osmotic dehydration process (OD) with the loss of water (WL) from the food to the solution and the gain of solids from the solution (SG) by the food. For this reason, OD is commonly used to produce semi-dehydrated or enriched foods by incorporation. Although the most of OD studies are focused on the WL and SG processes, many publications addresses the physicochemical and nutritional changes resulting from OD in the food matrix and in the osmotic solution. Such changes must be handled in order to improve the quality of the product. This work is a compilation of publications with this approach.

Phase I trial of ixabepilone administered as three oral doses each separated by 6 hours every 3 weeks in patients with advanced solid tumors.

BACKGROUND: Ixabepilone, which stabilizes microtubules, has low susceptibility to drug resistance mediated by P-glycoprotein or ßIII-tubulin. MATERIALS AND METHODS: This study was designed to determine the maximum tolerated dose (MTD) of oral ixabepilone when administered every 6 h for three doses, every 3 weeks, to patients with refractory advanced cancers. Eighteen patients were treated with escalating doses of ixabepilone: three at cohort 1 (30 mg/dose; 90 mg on Day 1), nine at cohort 2 (40 mg/dose; 120 mg on Day 1), and six at cohort 3 (50 mg/dose; 150 mg on Day 1). Serial plasma samples were collected during cycle 1 for pharmacokinetic (PK) measurements. RESULTS: Of the 18 treated patients, eight were male and ten were female. The median age was 59 years, and most had an excellent performance status (KPS 90-100; 61%). There were two dose limiting toxicities (DLT): Grade 4 febrile neutropenia at the 120 mg dose and Grade 4 neutropenic sepsis at the 150 mg dose. Because of the severity and duration of neutropenic sepsis at level 3, level 2 (120 mg) was defined as the MTD and this cohort was expanded to nine patients. High inter-individual variability in plasma drug concentrations was observed during the study, with particularly high levels in two patients with DLT. CONCLUSIONS: On the basis of this safety profile, the MTD of oral ixabepilone was defined as 120 mg given as three 40 mg doses each separated by 6 h on Day 1 of a 3-week cycle. However, the PK variability observed makes further development of this oral formulation unlikely.