Absorption of clonazepam after intranasal and buccal administration

Department of Clinical Pharmacy and Toxicology, Maasland Hospital, Sittard, The Netherlands.
British Journal of Clinical Pharmacology (Impact Factor: 3.88). 05/1995; 39(4):449-51. DOI: 10.1111/j.1365-2125.1995.tb04476.x
Source: PubMed


Serum concentrations of clonazepam after intranasal, buccal and intravenous administration were compared in a cross-over study in seven healthy male volunteers. Each subject received a 1.0 mg dose of clonazepam intranasally and buccally and 0.5 mg intravenously. A Cmax of 6.3 +/- 1.0 ng ml-1 (mean; +/- s.d.) was measured 17.5 min (median) (range 15-20 min) after intranasal administration. A second peak (4.6 +/- 1.3 ng ml-1) caused by oral absorption was seen after 1.7 h (range 0.7-3.0 h). After buccal administration a Cmax of 6.0 +/- 3.0 ng ml-1 was measured after 50 min (range 30-90 min) with a second peak of 6.5 +/- 2.5 ng ml-1 after 3.0 h (range 2.0-4.0 h). Two minutes after i.v. injection of 0.5 mg clonazepam the serum concentration was 27 +/- 18 ng ml-1. It is concluded that intranasal clonazepam is an alternative to buccal administration. However, the Cmax of clonazepam after intranasal administration is not high enough to recommend the intranasal route as an alternative to intravenous injection.

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    • "However, caregivers in The Netherlands are not qualified to administer parenteral medication, so this alternative is not feasible in the residential setting. Buccal clonazepam (Schols-Hendriks et al., 1995) and midazolam (Schwagmeier et al., 1998; Scott et al., 1999; Body & Ijaz, 2005; McIntyre et al., 2005) are effective as out-of-hospital treatment for seizure exacerbations, but hypersalivation, jerking movements of the jaw, or general restlessness may preclude the buccal route. Nasal lorazepam (Ahmad et al., 2006) and midazolam nasal drip (Kendall et al., 1997; Fisgin et al., 2000; Scheepers et al., 2000; Smith & Carley, 2005) have been proven effective in this situation. "
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