Dose tolerance and pharmacokinetic studies of pseudoephedrine sustained action capsules were performed in thirty-three adult male subjects who received either 120 mg or 150 mg capsules every twelve hours for seven consecutive days in a double-blind parallel design study. Although only one subject in the 150 mg group was discontinued prematurely from this study, a large number of side effects typical of CNS stimulation were seen. A placebo effect might account for a portion of these complaints, however symptoms evaluated as being due to drug were significantly more severe and persistent in the 150 mg group. Pulse rates showed a persistent and significant increase while systolic and diastolic blood pressure fell from the baseline values in both groups. A pharmacokinetic analysis of the pseudoephedrine plasma concentration-time data provided estimates of half-life and the volume of distribution/availability ratio. The values obtained were in good agreement with values reported by others. Half-life was not influenced by urine pH probably as a result of the narrow range of urine pHs observed in the subjects. Calculations of relative bioavailability suggest that the 120 mg capsule formulation has a 30% greater bioavailability compared to the 150 mg capsule.

In a recent comparison of estradiol and conjugated estrogen creams,6 single intravaginal doses of both estrogens were well absorbed by postmenopausal women. Only the estradiol cream led to plasma estrone and estradiol levels of premenopausal women. Symptoms of menopause have largely been attributed to a decrease in estrogen secretion, a normal process of aging. While the question of the best mode of therapy is controversial, physiological replacement would be a logical choice for postmenopausal vasomotor symptoms and vaginal mucosa atrophy. Our study was conducted to determine estrogen levels achieved after nightly vaginal administration of estradiol cream for 14 days and to evaluate it in the treatment of postmenopausal signs and symptoms. Materials and methodsThe patients were postmenopausal for at least 1 yr and had vasomotor or vaginal symptoms of estrogen deficiency. They received no estrogen or medications which could interfere with estrogen assays for at least 1 mo prior to the study. The study followed a double-blind parallel design. On a random assignment 20 patients received estradiol vaginal cream 0.01% (0.2 mg 17,8-estradiol) and 10 patients received conjugated estrogen cream (1.25 mg conjugated estrogens). An intravaginal dose of 2 gm of cream was administered at bedtime for 14 consecutive days. Patients returned for evaluation of their therapy on day 8 (12 hr after their seventh dose) and day 15 (12 hr after their fourteenth dose).Efficacy of the creams was measured by the maturation indices of the vaginal epithelium cells and severity ratings of vaginal and vasomotor symptoms at each visit. Patients were asked to record the number of vasomotor symptoms per day, and the severity of the hot flashes, 502

The bioavailability of digoxin (lanoxin) tablets, oral aqueous solution of digoxin, and capsules containing a solution of digoxin was compared with digoxin given intravenously over 1 and 3 hr. The mean peak serum concentration of digoxin after the 1-hr intravenous infusion was 5 ng/ml, after the 3-hr infusion, 3.5 ng/ml, and after the oral solution, 2.0 ng/ml. There was an equivalent bioavailability of the oral solution and reference tablets of digoxin. The digoxin in capsules tended to be better absorbed than the reference tablets. There was 21% more digoxin excreted over 6 days after the 3 hr iv infusion than after the 1 hr iv infusion. This indicates that the calculated bioavailability of an orally administered dose of digoxin may vary with the rapidity of injection of the intravenous standard. It is estimated that an oral tablet of digoxin of 0.5 mg has about the same bioavailability as 0.35 of digoxin given by slow intravenous infusion (or 0.4 mg if calculated against a rapid intravenous injection).

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