THE BIOAVAILABILITY OF DIAZEPAM FROM UNCOATED TABLETS IN HUMANS .2. EFFECT OF GASTRIC FLUID ACIDITY

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  • 1 January 1982
    • journal article
    • research article
    • Vol. 20  (4) , 166-170
Abstract
The healthy male volunteers participating in bioavailability tests of diazepam tablets were classified into 2 groups, high and low acidity groups, on the basis of the acidity of their gastric fluid. This was estimated by the Gastrotest method. The bioavailability parameters of 4 tablet preparations of diazepam (5 mg) after single administration were compared statistically between the 2 groups. Subjects with low acidity showed significantly lower diazepam serum levels than subjects with high acidity at 1 and/or 2 h after administration of tablets B, C and D, which showed slower rates of dissolution at pH 4.6. Tablet B gave a significantly lower peak concentration than the other tablets in the high acidity group; in the low acidity group tablet A gave a higher level than the other tablets. The peak concentrations in the low acidity group correlated well with the dissolution rates represented as 1/T70 (time of 70% dissolution) at pH 4.6, but a good method for determining the dissolution rates except for T50 values with the rotating flask method at pH 4.6 could not be found. These values significantly correlated with the peak concentrations of the high acidity group. The acidity of the gastric fluid affects the bioavailability of a drug such as diazepam, which has a pH-dependent dissolution rate and an especially slow rate of dissolution at pH 3-7.

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