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.

Reversed-phase paired-ion high-performance liquid chromatographic method for the separation and quantification of multiple bleomycin congeners.

A rapid, linear gradient chromatographic technique for separating and quantifying copper(II)-chelated bleomycin congeners is described. This method is also capable of separating divalent from trivalent metal chelates; determining the purity of many chemically modified bleomycins; and assaying bleomycin hydrolase activity on complex mixtures. Quantification at 280 nm is sensitive to 50 pmol and is linear at least up to 10 nmol per injection.