The safety and tolerability of zolpidem — an update

Abstract

Zolpidem belongs to a new class of hypnotic agents, chemically distinct from the pre-existing ones, and has a unique neuropharmacological profile. It induces sedative/hypnotic effects in rodents at doses much lower than those for anticonvulsant and myorelaxant activities. Clinically, zolpidem is indicated for the short term treatment of insomnia. It has a short half-life (2.4h), with no active metabolite, and does not accumulate during repeated administration. The pharmacokinetic profile associated with the absence of active metabolites is consistent with the short duration of action and absence of residual effects that have been observed. Polysomnographic experience indicates that zolpidem induces a sleep pattern which is similar to that of physiological sleep, and which produces either no or only minimal effects on sleep architecture after abrupt discontinuation. Aspects of the general safety of zolpidem have been studied in data obtained from healthy volunteers and patients, both adult and elderly, during its clinical development and in post-marketing experience. Zolpidem appears to be well-tolerated in adults and in the elderly, when administered in accordance with prescribing instructions. The available data indicate that, in these circumstances, the risk of abuse or dependence is minimal.

Long-lasting Modulation of Glutamatergic Transmission in VTA Dopamine Neurons after a Single Dose of Benzodiazepine Agonists

“…The GABA A receptor a1 subunit-preferring BZ-site ligand ZOL has less abuse liability than DZ (Darcourt et al, 1999;Hajak et al, 2003;Griffiths and Johnson, 2005). Here we found that ZOL at the dose (5 mg/kg) that acts specifically via a1 subunit-containing receptors (Crestani et al, 2000) increased the AMPA/NMDA ratio in VTA DA neurons.…”

Kinetics of Zolpidem and Its Metabolite after Single Dose Oral Administration

“…Zolpidem is recommended for the reduction of sleep onset time, increase total duration of sleep and sleep efficiency, given in doses of 5 up to 7.5 mg [1,6] for the short-term treatment of insomnia [7].…”

“…Is characterized by linear kinetics in the 5-20 mg dose range [5], is highly bound to plasma proteins (around 92%) [6] and it is subjected to extensive hepatic metabolism [7,8]. Zolpidem is a substrate to several distinct CYP 450 isoenzymes, among which the major metabolism pathway occurs through CYP3A4 (61%) [9,10,11].…”

Zolpidem-Induced Narcolepsy, Faint, Seizure or Coma? A Case Report

“…Although ZLP appears to be well-tolerated in adults and the elderly [4], there is a host of reports of its abuse, dependence and withdrawal syndrome. It is worth mentioning that in the majority of these reported cases, the recommended dose of ZLP is exceeded and most of the patients have a history of substance How to cite this paper: Parsa, A., Mohammadkhan, A. and Babaeian, M. (2017) Zolpidem-Induced Narcolepsy, Faint, Seizu-abuse and/or psychiatric disorder [5] [6].…”