Abstract

We present the results of a pilot study where five commercial drugs were analyzed using a fast and cost effective method to assess and compare their tissue distribution. We propose this technique as an aid for decision making in late stage lead optimization.

Amlodipine, Propranolol, Paracetamol (Acetaminophen), Diphenhydramine and Lisinopril were radiolabelled with tritium. Each labelled compound was dosed orally to two male mice(CD1). At two time points the mice were killed and sections prepared for autoradiography. The sections were analyzed using a real-time digital autoradiography imaging system. The autoradiography imaging system is based on gas detection and allows for the rapid real-time acquisition of autoradiography images. The signal of each disintegration is detected independently, thereby offering precise and rapid quantification of radio-distribution.

Images comparable with those obtained using the traditional approach of phosphor-storage plates and a 2 week exposure time were obtained after just 18 hours). Results were consistent with known distribution parameters for all compounds analysed. Using Tmax and a later time for analysis gave an indication of the rate of elimination from tissues, and enabled identification of potential accumulation/retention in target tissues.