In Vivo Intravenous Pharmacokinetic Study in Rats

Animal studies were approved by the Institutional Animal Care and Use Committee (IACUC) of Genentech and in accordance with federal guidelines. A total of 9 Sprague Dawley rats weighing ~ 250 to 310 g were acquired from Charles River Labs (Wilmington, MA, USA) and divided evenly into 3 treatment groups (2 females, 1 male per group). Each group was intravenously administered 5 mg/kg of curcumin in either liposome, lipodisk, or solution form by IV bolus through a jugular vein cannula. Blood collection was performed at the following time points: predose, 2 min (0.033 h), 5 min (0.083 h), 15 min (0.25 h), 30 min (0.5 h), and 1, 2, 4, 8, 24 and 48-h post-dose. All samples were collected through a femoral artery cannula by a Culex automated blood sampling machine (West Lafayette, IN, USA) and placed in tubes containing K2 EDTA. Blood samples were centrifuged for 5 min at 3700 rpm (2235 G’s) for plasma collection.

Drug plasma concentrations were quantified via LC/MS/MS. For this analysis, plasma concentrations were measured by a liquid chromatographic-tandem mass spectrometry (LC/MS/MS) assay method with an internal standard.