indicated by peak and area-under-the-curve levels is linear across a dose range of 25 to 100mg. Food increases the bioavailability of alpidem by 15 to 20%. Distribution Alpidem is a highly lipophilic compound and in animals is extensively distributed into lipid-rich tissues. Similarly, alpidem has been shown to cross the blood–brain barrier in animals, and showed a brain/plasma ratio of about 2.0 to 2.5 following systemic administration. This is related to significantly slower efflux of alpidem from the brain than entry. The active metabolites of alpidem are also brain-penetrant, although occur in the brain at levels lower than those of alpidem. Alpidem may be concentrated more in lipid-rich white matter brain structures than grey matter structures. In humans, the volume of distribution of alpidem is large at 8.7L•kg-1. The plasma protein binding of alpidem is 99.4%, with similar isolated fractions bound to albumin (97.0%) and α1-acid glycoprotein (97.3%). The free fraction of alpidem is slightly higher in people with cirrhosis (0.86 ± 0.06%) and renal failure (0.72 ± 0.03%) relative to normal individuals (0.61 ± 0.05%). Metabolism Alpidem is extensively metabolized, including by hydroxylation, dealkylation, and conjugation. Many metabolites of alpidem have been identified, and some of these metabolites may contribute to its pharmacological activity. Elimination Alpidem is eliminated mainly in feces, with less than 0.1% excreted in urine. A majority of alpidem is eliminated within 48 to 72hours following oral dosing. Only trace amounts of unchanged alpidem are found in feces and urine. The metabolites of alpidem are excreted mainly in via the bile in feces, with less than 5% eliminated via urine. The elimination half-life of alpidem was mean 18.8 ± 0.8hours (range 7 to 44hours) following a single 50-mg oral dose given to young individuals. In elderly individuals, a trend toward a longer half-life was observed (22.6 ± 2.3hours). Conversely, in children age 8 to 12years, the half-life of alpidem was considerably reduced (11.4 ± 1.9hours). The half-lives of alpidem and its metabolites are significantly prolonged in people with hepatic impairment. Conversely, the half-lives of alpidem and its metabolites were unchanged in people with different stages of renal impairment, though plasma concentrations were significantly increased. The clearance of alpidem was estimated to be 0.86 ± 0.04L•h-1•kg-1 in healthy individuals. Chemistry Alpidem is a nonbenzodiazepine, and hence is not structurally related to benzodiazepines. It is a member of the imidazopyridine group of compounds. Alpidem is structurally related to