title: The effect of experimentally induced sleep disturbance on the pharmacokinetics of lorazepam in healthy volunteers.
abstract: The aim of this study was to evaluate the effect of sleep disturbance on the pharmacokinetics, especially on the absorption, of lorazepam in humans. Eight healthy male volunteers received a single oral dose of lorazepam 1 mg before sleep on two occasions in a cross-over design. In either of the two doses, subjects were intermittently exposed to noise for 1.5 hours after oral lorazepam administration. Plasma lorazepam concentrations were measured by HPLC. The exposure to noise significantly prolonged tmax (control vs. noise: 2.0 vs. 3.0 hours) and significantly decreased AUC of lorazepam in the absorption phase. The reduction was 54% (95% CI, 15 - 75%) and 24% (3 - 40%) for AUC (0 - 1 hours) and AUC (0 - 3 hours), respectively. No significant changes were observed in other pharmacokinetic parameters. The results of this study suggest that the onset of drug action after oral lorazepam administration can be altered by sleep disturbance.
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Kotegawa
authors.forename: Kimiko
authors.initials: K
authors.lastname: Tsutsumi
authors.forename: Hiromitsu
authors.initials: H
authors.lastname: Imai
authors.forename: Kyoichi
authors.initials: K
authors.lastname: Ohashi
authors.forename: Shigeyuki
authors.initials: S
authors.lastname: Nakano
mesh_terms: D000284:Administration, Oral; D000328:Adult; D019540:Area Under Curve; D002851:Chromatography, High Pressure Liquid; D018592:Cross-Over Studies; D006207:Half-Life; D064368:Healthy Volunteers; D006801:Humans; D006993:Hypnotics and Sedatives / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D007408:Intestinal Absorption; D008140:Lorazepam / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D008297:Male; D009622:Noise / Q000009:adverse effects; D012890:Sleep; D012893:Sleep Wake Disorders / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D055815:Young Adult
chemical_list: D006993:Hypnotics and Sedatives; D008140:Lorazepam