CLINICAL PHARMACOKINETICS AND PHARMACODYNAMICS OF ZOLPIDEM - THERAPEUTIC IMPLICATIONS

Zolpidem is an imidazopyridine which differs in structure from the ben zodiazepines and zopiclone. It is a strong sedative with only minor an xiolytic, myorelaxant and anticonvulsant properties, and has been show n to be effective in inducing and maintaining sleep in adults. The ava ilable evidence suggests that zolpidem produces no rebound or withdraw al effects, and patients have experienced good daytime alertness. Zolp idem 10mg in non-elderly and a reduced dose of 5mg in elderly individu als are clinically effective. In humans, the major metabolic routes in clude oxidation and hydroxylation; none of the metabolites appears to be pharmacologically active. The pharmacological activity of zolpidem results from selective binding to the central benzodiazepine receptors of the or subtype. Zolpidem is approximately 92% bound to plasma prot eins; absolute bioavailability of zolpidem is about 70%. After single 20mg oral doses, typical values of pharmacokinetic variables for zolpi dem in humans are: a peak plasma concentration of 192 to 324 mu g/L oc curring 0.75 to 2.6 hours postdose; a terminal elimination half-life o f 1.5 to 3.2 hours; and total clearance of 0.24 to 0.27 ml/min/kg. Zol pidem pharmacokinetics are unchanged during multiple-dose treatment.Zo lpidem pharmacokinetics are not significantly influenced by gender. Cl earance of zolpidem in children is 3 times higher than in young adults , and is lower in very elderly people. There are no significant differ ences in the pharmacokinetic parameters between various racial groups. Dosage reduction appears to be prudent in patients with renal disease , and caution should be exercised when prescribing zolpidem to; elderl y patients with hepatic impairment. Coadministration of haloperidol, c imetidine, ranitidine, chlorpromazine, warfarin, digoxin or flumazenil do not alter the pharmacokinetics of zolpidem; flumazenil predictably antagonises the hypnotic effects of zolpidem. Alertness tends to be r educed when cimetidine is combined with zolpidem. Volunteers treated w ith imipramine plus zolpidem developed anterograde amnesia.