Comparison of meclizine levels in the plasma of rats and dogs after intranasal, intravenous, and oral administration.
Meclizine, used prophylactically for the prevention of motion sickness and vertigo, is presently available only in oral form. We report herein that, when given intranasally, meclizine dihydrochloride is absorbed in rats about half as effectively as when given intravenously, but about six times more effectively than after oral administration, as estimated by the area under the plasma concentration-time curve. The mean times to peak levels in plasma are about 8.5 min after an intranasal dose and 49.0 min after oral delivery. We extended these studies to a second species, the beagle dog, and achieved qualitatively similar results with a new formulation (Mecnazone; Nastech Pharmaceutical Co., Inc.). The fraction absorbed intranasally was about 0.89 that of an equivalent intravenous dose but about four times that of an equivalent oral administration. In these studies, the mean times to peak levels in plasma was 11.9 min after an intranasal dose and 70.0 min after an oral dose. Terminal elimination kinetics were the same for all routes within each species. Intranasal delivery of meclizine therefore appears to be superior to the oral route for the more rapid achievement of substantial levels in plasma at a reduced dose.
D000281:Administration, Intranasal; D000284:Administration, Oral; D000818:Animals; D002851:Chromatography, High Pressure Liquid; D004285:Dogs; D007275:Injections, Intravenous; D007700:Kinetics; D008468:Meclizine / Q000008:administration & dosage / Q000097:blood*; D051381:Rats; D013045:Species Specificity
D008468:Meclizine