Studies of nontarget-mediated distribution of human full-length IgG1 antibody and its FAb fragment in cardiovascular and metabolic-related tissues.

Tissue distribution and pharmacokinetics (PK) of full-length nontargeted antibody and its antigen-binding fragment (FAb) were evaluated for a range of tissues primarily of interest for cardiovascular and metabolic diseases. Mice were intravenously injected with a dose of 10 mg/kg of either human IgG1or its FAb fragment; perfused tissues were collected at a range of time points over 3 weeks for the human IgG1 antibody and 1 week for the human FAb antibody. Tissues were homogenized and antibody concentrations were measured by specific immunoassays on the Gyros system.

Assessment of interaction potential of AZD2066 using in vitro metabolism tools, physiologically based pharmacokinetic modelling and in vivo cocktail data.

Purpose: Static and dynamic (PBPK) prediction models were applied to estimate the drug-drug interaction (DDI) risk of AZD2066. The predictions were compared to the results of an in vivo cocktail study. Various in vivo measures for tolbutamide as a probe agent for cytochrome P450 2C9 (CYP2C9) were also compared.