Absorption of aluminum from aceglutamide aluminum in healthy adult males.

The absorption of aluminum was studied in twelve healthy male volunteers over a period of fourteen days in a placebo-controlled, double blind study. All subjects were institutionalized during the study. Eight subjects (treated group) received ascending doses of aceglutamide aluminum (N-acetyl-L-glutamine aluminum complex) administered in multiple daily doses. The remaining four subjects (untreated group) received placebo. Systemic absorption and excretion of aluminum were evaluated by measuring aluminum concentrations in serum, urine and fecal samples. Aluminum concentrations were determined by electrothermal atomic absorption spectrometry. All serum aluminum concentrations were less than 16 micrograms/L for both groups. The mean urinary and fecal aluminum concentrations in the aluminum-treated group were significantly higher than in the untreated group during the study days the drug was administered. The total amount of aluminum (as aceglutamide aluminum) given to each treated subject during the 14 day study period as 3290 mg. The mean total fecal aluminum concentration was 3318 mg for the treated group and 269 mg for the untreated group during the study period. These findings are consistent with the view that some aluminum absorption from the gastrointestinal tract occurred following the administration of the drug. The absorbed aluminum appears to have been rapidly excreted in the urine and the feces.

Endoscopic evaluation of slow-release potassium chloride preparations.

In a double-blind, randomized, placebo-controlled clinical trial, 30 healthy subjects took one of two potassium chloride preparations or placebo three times a day for 1 week with concomitant oral glycopyrrolate dosing. The upper digestive tract was endoscopically examined immediately before and after the treatment period. One subject in both of the KCl treatment groups and six subjects in the placebo group developed submucosal lesions. All lesions were minor and of limited clinical significance. There may be reason to believe that glycopyrrolate plays a role in the production of such lesions. If so, the concomitant use of glycopyrrolate in clinical trials of KCl preparations may cloud the results of such studies.

Dynamics of propranolol dosing schedules.

Kinetic and dynamic data from 27 healthy male subjects were evaluated in a double-blind, randomized, double-crossover study to test the hypothesis that 180 mg/day propranolol twice and three times a day would provide much the same plasma levels and beta 1-blockade. The data indicate that propranolol twice rather than three times a day should be favored when beta 1-blockade is needed in therapy. The dynamic efficacy of the two schedules was the same and maximum concentration, AUC0-24, and 0-hr plasma propranolol values were higher after twice-than after three-times-daily dosing. The degree of beta 1-blockade (reduction in exercise tachycardia) was much the same on both dosing regimens at trough concentrations. These data indicate that both twice- and three-times-a-day dosing schedules provide well-sustained 24-hr beta-blockade and are probably interchangeable for therapeutic purposes.

Use of difenoximide (SC-26100) for narcotic detoxification: a preliminary tolerance and efficacy study.

Difenoximide (SC-26100) is closely related to the antidiarrheal agent, diphenoxylate, which is a chemical congener of meperidine. It has been shown to have a greater ability than methadone to suppress opiate withdrawal in addicted mice, and it has produced less physical dependence than morphine and methadone in laboratory animals. In this study difenoximide was administered to nine active heroin addicts. A dose of 4 mg administered 4 times per day for 3 days effectively suppressed opiate withdrawal, while a dose of 8 mg produced symptoms resembling those of narcotic excess in subjects who had recently self-administered heroin. No side effect were observed at the therapeutic dosage level, and the drug was well accepted by subjects. Difenoximide was shown to be a potentially useful narcotic treatment agent in this impatient study.