Disposition of premazepam, an anti-anxiety pyrrolodiazepine, in the cynomolgus monkey.

The plasma levels, tissue distribution and the urinary elimination of total radioactivity and of unchanged premazepam were determined in cynomolgus monkeys given intravenously the 14C labelled pyrrolo diazepine. Following the i.v. injection, both total 14C and the unchanged drug disappeared from the central compartment in a biphasic manner with terminal half-lives of 11.9 and 3.7 h respectively. Elimination occurred mainly via the kidneys with 58% of the administered 14C and 16% of premazepam recovered in 48 h. Tissue distribution of radioactivity (whole-body autoradiography) showed as target tissues the emunctory organs and the melanin rich choroid of the eyes and the traiv follicles. Interestingly, five min after the i.v. dose the distribution of premazepam in the brain indicated an homogeneous diffusion in the different areas with a preferential affinity for the grey matter.