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Ten healthy male volunteers received chlordiazepoxide (CDX) hydrochloride or matching placebo with Maalox or water in a four-way single-dose crossover trial. Coadministration of CDX with Maalox did not change the completeness of CDX absorption but significantly slowed its rate of absorption and the rate of desmethylchlordiazepoxide (DMCDX) appearance. Self-rating of feeling "spacey" at 1.0 and 2.5 hours were significantly increased over baseline for CDX taken with water but not with Maalox. Increases in "spacey" feelings at 1.0 hours were highly correlated with 0.5-hour but not with 1.0-hour blood levels. Similar findings were observed for self-ratings of "thinking" slowed down. Thus certain subjective effects of antianxiety agents after oral dosage may depend on the rate of drug absorption and may be attenuated or eliminated if the absorption rate is reduced.
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