Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0018681 (headache)
 56,091 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Zaleplon is a pyrazolopyrimidine hypnotic agent which is indicated for the short term (2 to 4 weeks) management of insomnia. Zaleplon 5 and 10 mg at bedtime (usual recommended doses) significantly reduced sleep latency compared with placebo in clinical trials in nonelderly and elderly patients with insomnia. In general, sleep maintenance (sleep duration and number of awakenings) and sleep quality were not significantly different from placebo with zaleplon 5 and 10 mg/night. Zaleplon 20 mg/night significantly improved sleep latency and duration in nonelderly patients, but effects on number of awakenings were inconsistent and sleep quality generally did not improve. The relative hypnotic efficacy of zaleplon compared with that of triazolam and zolpidem is not yet clearly established. Tolerance to the hypnotic effects of zaleplon generally did not occur during 5 weeks' treatment, or during long term treatment (6 or 12 months) according to a small number of studies presented as abstracts. Zaleplon was well tolerated in clinical trials. The most common event was headache but the incidence was similar to that observed with placebo. Zaleplon 5 and 10 mg did not impair psychomotor function or memory even immediately after the dose in studies in volunteers or patients with insomnia. Zaleplon 20 mg, however, impaired psychomotor function and memory immediately after the dose but next-day effects were not observed. The psychomotor profile of zaleplon appears to be better than that of comparator agents. Rebound insomnia was not observed after sudden discontinuation of up to 12 months' treatment with zaleplon 5 and 10 mg/night and up to 4 weeks' treatment with zaleplon 20 mg/night. In addition, the potential for withdrawal syndrome with zaleplon appears to be low according to limited data. In conclusion, zaleplon 5, 10 and 20 mg administered at bedtime, or later if patients have difficulty sleeping, is an effective and well tolerated hypnotic agent. There was no evidence of next-day residual effects with the 5 and 10 mg dosages, and the incidence of withdrawal effects with zaleplon 5, 10 and 20 mg did not differ significantly to that observed with placebo. In addition, tolerance to the effects of zaleplon is unlikely to develop when administered for the recommended treatment period. The comparative efficacy and tolerability of zaleplon with other short acting nonbenzodiazepine hypnotics is difficult to establish. However, on the basis of current efficacy evidence and the lower incidence of residual effects with zaleplon 5 and 10 mg relative to comparator agents, this drug represents a useful option in the management of patients with insomnia who have difficulties initiating sleep.
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PMID:Zaleplon: a review of its use in the treatment of insomnia. 1098 40

Pharmacokinetics, pharmacodynamics, safety, and tolerability of inhaled zaleplon were assessed in healthy volunteers. Forty participants received 0.5, 1, 2, or 4 mg zaleplon or placebo as a thermally generated aerosol in a randomized, double-blind, parallel-group, dose escalation study. Blood was collected up to 24 hours after dosing, and sedation was assessed up to 8 hours. Following inhalation, the observed median time to maximum plasma concentrations (25%, 75%) was 1.89 (1.45, 3.08) minutes and the mean (SD) elimination half-life was 1.24 (0.24) hours. The equilibration half-life for sedation (t(1/2) k(e0) ) was 1.16 (0.62, 2.17) minutes. The zaleplon AUC was dose proportional across doses, with a slope (90% confidence interval) of log-AUC versus log-dose of 0.92 (0.82, 1.02). No clinically significant changes were noted in laboratory values, vital signs, or spirometry. The most common adverse events were dizziness, somnolence, euphoria, headache, and visual disturbance. Zaleplon inhalation represents a safe, well-tolerated means of rapidly achieving effective plasma concentrations.
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PMID:The pharmacokinetics and pharmacodynamics of zaleplon delivered as a thermally generated aerosol in a single breath to volunteers. 2343 59