Diazepam absorption: Effect of antacids and food

Abstract

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.

The effects of omeprazole-induced hypochlorhydria on absorption of theophylline from a sustained-release formulation

“…The gastrointestinal absorption of isoniazid in man is delayed and depressed by aluminium hydroxide gel [2], while the absorption of sulphadiazine, quinine and pentobarbital in rats is retarded by both magnesium and aluminium hydroxides [3,4]. However, in man, while a magnesium aluminium mixture delays diazepam absorption [5], the concurrent administration of aluminium hydroxide gel or hydrated magnesium aluminate has no effect on ampicillin absorption [6]. In the case of sodium bicarbonate, solutions of which leave the stomach more rapidly than plain water [7], the influence of high concentrations of electrolytes within the gastrointestinal tract can not be discounted.…”

The effects of food on drug bioavailability.

“…This may be because residence time and fluid volume are greater producing better dissolution (Greenblatt et al, 1978). In particular, poorly water soluble drugs (e.g.…”

Effect of food on the bioavailability of adinazolam from a sustained release formulation: Effect of meal timing and lack of dose dumping

“…Venous blood samples (7 ml) were collected immediately prior to drug dosing and at 0-5, 1.0, 1.5, 2.0, 3,4,6,8,10,12,16,20,24,30, and 36h after the dose.…”