Expanded clinical evaluation of lovastatin (EXCEL) study results. II. Assessment of the human lens after 48 weeks of treatment with lovastatin.

The crystalline lenses of hypercholesterolemic patients were assessed before and after 48 weeks of treatment with lovastatin or placebo to determine the effect of lovastatin on the human lens. Patients were given a biomicroscopic (slit-lamp) examination of the lens, and a previously validated, standardized classification system was used to describe the findings. A total of 8,245 patients were randomly assigned in equal numbers to treatment with placebo or lovastatin 20 or 40 mg once or twice daily in this double-blind, parallel-group study. Statistical analyses of the distribution of cortical, nuclear and subcapsular opacities at 48 weeks, adjusted for age and presence of an opacity at baseline, showed no significant differences (p less than 0.01) between the placebo and lovastatin-treated groups. Visual acuity assessments at week 48 were also not found to have significantly different distributions among treatment groups. Moreover, no significant differences were found among the groups in the frequencies of greater than or equal to 2-line worsening in visual acuity with concurrent progression in lenticular opacity, cataract extraction, or any spontaneously reported adverse ophthalmologic experience. No evidence was found for an effect of lovastatin on the human lens after 48 weeks of treatment.

MK-208, a novel histamine H2-receptor inhibitor with prolonged antisecretory effect.

MK-208 is a guanidinothiazole derivative reported to be a potent H2 blocker devoid of antiandrogenic activity. Its potency and duration of action, in inhibiting pentagastrin-stimulated gastric secretion in man, was evaluated in this double-blind, five-way cross-over trial. Ten healthy male volunteers received single oral doses of placebo, cimetidine 300 mg, and MK-208 5, 10, and 20 mg. A continuous intravenous infusion of pentagastrin (1 microgram/kg/hr) was given 2-4 and 5-7 hr after each oral dose. Gastric contents were continuously aspirated and volumes and acid content determined every 30 min. Plasma levels for MK-208 and cimetidine were monitored over the 7 hr of the study. Cimetidine and all doses of MK-208 significantly inhibited gastric acid secretion in the initial 2-4 hr; however, 10- and 20-mg doses of MK-208 were significantly more potent than cimetidine. In the 5- to 7-hr period, cimetidine 300 mg was not different from placebo, while MK-208 in all doses studied continued to significantly suppress gastric secretion. Plasma levels for MK-208 showed dose-related increments. The results suggest that: (1) MK-208 is a potent inhibitor of gastric secretion in man, in a dose-related fashion at the doses tested; (2) under the study conditions, 5 mg MK-208 was equipotent to 300 mg cimetidine but with greater duration of action, extending at least 7 hr; and (3) these data suggest a future role for this new agent in therapy for acid-peptic disease in man.