High-throughput pharmacokinetic method: Cassette dosing in mice associated with minuscule serial bleedings and LC/MS/MS analysis

A method for pharmacokinetic studies using cassette dosing associated with serial bleeding in mice is described. PK profiles of four soluble epoxide hydrolase inhibitors were determined following oral, subcutaneous or intraperitoneal administration individually or in cassette dosing. Parent analyses were performed on only 5 mu L of whole blood from serial bleeds (up to 10 per animal), by LC/MS/MS. An accuracy (88-100%) and precision (< 10% RSD) were observed, leading to reliable datum points for PK calculation. PK profiles, T-max, C-max and half-life values after cassette dosing were similar to the individual PK results. This method dramatically increases speed of data collection while dramatically reducing cost and animal usage. The results presented here clearly indicate that this proposed method could be applicable to high-throughput PK studies. (c) 2005 Elsevier B.V. All rights reserved.