The fact that vitamin A is absorbed via the lymphatic route was first demonstrated by Drummond, Bell, and Palmer in 1935, in studies carried out in a patient with chylothorax (2). Since then this finding has been confirmed and amplified by studies with other animal species. It has been well established that retinol 1 is largely esterified during its intestinal absorption, and partial information about the processes of absorption and esterification has been available from the studies of Ganguly and his associates (3-5) and Pollard and Bieri (6). In contrast to retinol, however, much less detailed information has been available concerning the intestinal absorption and metabolism of the provitamin A, ,8-carotene.Detailed studies of the events occurring during
4-Methylpyrazole (4-MP), an inhibitor of alcohol dehydrogenase, is a possible future drug for the treatment of methanol and ethylene glycol intoxications and the severe ethanol-disulfiram reaction. Therefore a placebo-controlled, double-blind, single-dose, randomized, sequential, ascending-dose "Phase I study" was performed in healthy volunteers in order to determine the tolerance of 4-MP at dose levels of 10 (n = 4), 20 (n = 4), 50 (n = 4), and 100 mg/kg (n = 3). Along with each dose group, there were two placebos except with the 100 mg/kg group where there was only one placebo. In the 10 and 20 mg/kg group there were no side-effects in any subject. At the 50 mg/kg level, three out of four subjects experienced slight to moderate nausea and dizziness from 0 to 2.5 h after dosing. In the 100 mg/kg group all three subjects reported side-effects like nausea, dizziness, and vertigo, that were short-lived in two subjects, but lasted up to 30 h in one subject. The study was stopped after evaluation of the latter subject, so fewer subjects were completed in this last group. Despite these subjective side-effects, there were no significant changes in objective clinical parameters like pulse, blood pressure, body temperature, or blood and urine chemistries. We conclude that at a single dose of 4-MP (10-20 mg/kg) producing plasma levels within a probable therapeutic range, no side-effects were attributed to 4-MP.
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