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Diazepam absorption: Effect of antacids and food
Author(s) -
Greenblatt David J.,
Allen Marcia Divoll,
MacLaughlin Dean S.,
Harmatz Jerold S.,
Shader Richard I.
Publication year - 1978
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1002/cpt1978245600
Subject(s) - diazepam , antacid , chemistry , absorption (acoustics) , pharmacokinetics , oral administration , crossover study , pharmacology , chromatography , medicine , biochemistry , materials science , alternative medicine , pathology , composite material , placebo
Nine healthy fasting volunteers received 5 mg of diazepam orally with 60 ml of water, 60 ml of magnesium aluminum hydroxide mixture (Maalox), or 60 ml of aluminum hydroxide trisilicate mixture (Gelusil) in a randomized, single‐dose, three‐way crossover study. Plasma concentrations of diazepam and its major metabolite (desmethyldiazepam) in multiple samples drawn during 48 hr after each dose were determined by electron‐capture gas‐liquid chromatography. Compared with the water treatment condition, administration of diazepam with each antacid yielded lower peak plasma concentrations which were attained later after the dose, longer lag times prior to the start of absorption, and prolongation of the absorption half‐life. Completeness of diazepam absorption, judged by the area under the 48‐hr plasma concentration curve (AUC‐48), was not influenced. In a second study, 6 of the subjects took diazepam after a standard breakfast. Diazepam absorption was slowed to an even greater extent than in the diazepam‐antacid treatment conditions. However, AUC‐48 averaged 26% more in the diazepam‐food condition than with the diazepam water condition suggestive of enhanced absorption. Under the conditions of this study, coadministration of diazepam with antacids or a standard meal reduces the rate of absorption but does not reduce extent of absorption.