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Bioavailability and Pharmacokinetics of Lorazepam after Intranasal, Intravenous, and Intramuscular Administration
Author(s) -
Wermeling Daniel Paul H.,
Miller Jodi Lynn,
Archer Sanford Mitchell,
Manaligod Jose M.,
Rudy Anita C.
Publication year - 2001
Publication title -
the journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.92
H-Index - 116
eISSN - 1552-4604
pISSN - 0091-2700
DOI - 10.1177/00912700122012779
Subject(s) - nasal administration , pharmacokinetics , lorazepam , bioavailability , medicine , crossover study , anesthesia , route of administration , pharmacology , absorption (acoustics) , physics , alternative medicine , pathology , acoustics , placebo
The purpose of this study was to evaluate the pharmacokinetic profile of intranasal lorazepam in comparison to currently established administration routes. Eleven healthy volunteers completed this randomized crossover study. On three occasions, each separated by a 1‐week washout, subjects received a 2 mg dose of lorazepam via the intranasal, intravenous, or intramuscular route. Blood samples were collected serially from 0 to 36 hours. Noncompartmental methods were used to determine pharmacokinetic parameters. Lorazepam was well absorbed following intranasal administration with a mean (%CV) bioavailability of 77.7 (11.1). Intranasal administration resulted in a faster absorption rate than intramuscular administration. Elimination profiles were comparable between all three routes. The concentration‐time profile for intranasal delivery demonstrated evidence of a double peak in several subjects, suggesting partial oral absorption. Females were found to have significantly higher AUC values than males for all three delivery routes. Overall, this study demonstrated favorable pharmacokinetics of intranasal lorazepam in relation to standard administration methods. Intranasal delivery could provide an alternative, noninvasive delivery route for lorazepam.