A double-blind controlled, randomized, parallel, multicenter 12-week study was conducted to compare the antihypertensive efficacy of lisinopril with that of metoprolol in treatment of moderate to severe hypertension. Initially, 118 patients were recruited on lisinopril and 61 on metoprolol; and for the purpose of efficacy analysis at week 8, 115 patients on lisinopril and 60 on metoprolol were included. The doses of lisinopril or metoprolol were 40-80 mg/day and 100-200 mg/day, respectively. At week 4, the pretreatment diastolic blood pressure of 111 mm Hg was decreased to 97 mm Hg (p less than 0.01) with lisinopril: metoprolol decreased the diastolic blood pressure from 110 to 99 mm Hg (p less than 0.01). Similar decreases were noted at week 8; however, the drop in blood pressure with lisinopril was not significantly different from that with metoprolol. Systolic blood pressure also demonstrated a decrease of about 18 mm Hg with lisinopril and 12 mm Hg with metoprolol (p less than 0.01). This larger decrease in systolic blood pressure with lisinopril was statistically significant at week 4 (p less than 0.05). These decreases in systolic blood pressures were maintained at week 8, again with statistical significance (p less than 0.01). Of the 118 lisinopril-treated patients, four were discontinued from lisinopril therapy because of headache, dizziness, rash, flushing, or lymphadenopathy. Four patients out of 61 (9.8%) were discontinued from metoprolol therapy because of fatigue, somnolence, asthenia, weight gain, flatulence, tremor, or bronchospasm. In conclusion, lisinopril 40-80 mg once daily is as effective as metoprolol 100-200 mg once daily in reducing diastolic blood pressure in patients with moderate to severe hypertension.(ABSTRACT TRUNCATED AT 250 WORDS)
The anabolic effects of bolasterone have been compared with other such agents and with a placebo by the use of a twin crossover method. By expressing human metabolic balance effects as differences between pretreatment and posttreatment nitrogen excretion values, the steroid was found to be 25 times as potent as fluoxymesterone, 80 times as effective as norethandrolone, and twice as effective as methandrostenolone. The anabolic effect of bolasterone was confirmed by a weight gain study which compared a placebo, a standard anabolic agent, and the test drug. Androgenic effects of bolasterone were not observed in these studies.
Arminone was given to 18 healthy subjects in doses of 75, 150, and 225 mg in a randomized crossover design. Plasma levels were shown to rise in proportion to dose. The mean plasma AUC, extrapolated to infinite time, was determined for each dose level; the values obtained were 4, 8.18, and 12.35 μg · hr/ml for the 75-, 150-, and 225-mg doses. Mean maximum observed plasma concentrations were 1.03, 1.74, and 2.58 μg/ml. At higher doses the extrapolated AUC is more variable, but it is linear over the range of 0.73 to 3.81 mg/kg. The apparent first-order terminal elimination rate is not dose dependent and corresponds to a t½ of 3.85 hr. Clinical Pharmacology and Therapeutics (1983) 34, 190–194; doi:10.1038/clpt.1983.151
This double-blind, randomized, parallel, placebo-controlled study evaluated the analgesic effects of single oral doses of 30 mg nalbuphine, 650 mg acetaminophen, and the contribution of each to the efficacy of their combination in 128 hospitalized patients with postoperative pain. Subjective reports of patients evaluated each hour for 6 hours were used as indices of analgesic response. Both nalbuphine and acetaminophen were significantly superior to placebo for most measures of total and peak analgesia. The interaction contrast between nalbuphine and acetaminophen was not significant for any analgesic measurements, indicating an additive effect of the components. The combination was the most effective treatment, followed by nalbuphine, acetaminophen, and placebo. Effects of the combination were significantly different from those of acetaminophen at 4, 5, and 6 hours and from those of placebo at 1 to 6 hours. There was no significant difference in the frequency or intensity of side effects among the groups. The combination of nalbuphine and acetaminophen appears to be a therapeutically useful combination.
Clinical Pharmacology and Therapeutics (1986) 39, 295–299; doi:10.1038/clpt.1986.42
Obesity is a highly prevalent medical condition and is commonly accompanied by hypertension. This study assessed the efficacy and safety of treatment with sibutramine hydrochloride for promoting and maintaining weight loss in obese patients with controlled hypertension, including a subset analysis of African American patients.
Patients and Methods
Obese patients with a body mass index (BMI, calculated as weight in kilograms divided by the square of height in meters) between 27 and 40 and a history of hypertension controlled with a calcium channel blocker (with or without concomitant thiazide diuretic treatment) were randomized to receive sibutramine (n = 150) or placebo (n = 74) with minimal behavioral intervention for 52 weeks. African Americans constituted 36% of enrolled patients. Efficacy assessments were body weight and related parameters (BMI and waist and hip circumferences), metabolic parameters (serum levels of triglycerides, high-density lipoprotein cholesterol [HDL-C], low-density lipoprotein cholesterol [LDL-C], total cholesterol, glucose, and uric acid), and quality-of-life measures. Safety assessments included recording of blood pressure, pulse rate, adverse events, and reasons for discontinuation.
Results
For patients receiving sibutramine, weight loss occurred during the first 6 months of the trial and was maintained to the end of the 12-month treatment period. Among patients receiving sibutramine, 40.1% lost 5% or more of body weight (5% responders) and 13.4% lost 10% or more of body weight (10% responders) compared with 8.7% and 4.3% of patients in the placebo group, respectively (P<.05). Changes in body weight were similar among African Americans and whites. Sibutramine-induced weight loss was associated with significant improvements in serum levels of triglycerides, HDL-C, glucose, and uric acid. Waist circumference and quality-of-life measures also improved significantly in patients receiving sibutramine. Sibutramine-treated patients had small but statistically significant mean increases in diastolic blood pressure (2.0 mm Hg) and pulse rate (4.9 beats/min) compared with placebo-treated patients (–1.3 mm Hg and 0.0 beats/min;P<.05); these changes were similar among African Americans and whites. Most adverse events were mild to moderate in severity and transient. The most common adverse event resulting in discontinuation among patients receiving sibutramine was hypertension (5.3% of patients receiving sibutramine vs 1.4% of patients receiving placebo).
Conclusions
In obese patients with controlled hypertension, sibutramine was an effective and well-tolerated treatment for weight loss and maintenance. Sibutramine-induced weight loss resulted in improvements in serum levels of triglycerides, HDL-C, uric acid, and glucose, and in waist circumference and quality-of-life measures. Blood pressure and heart rate increased by a small amount. Efficacy and safety profiles for sibutramine among African American and white obese patients with controlled hypertension were similar.
A castor oil model of induced diarrhea was used to evaluate dose regimens of the standard antidiarrheal polycarbophil. The study population consisted of 100 healthy volunteers, divided into five groups of 20 each, in whom diarrhea was induced by 120 ml flavored 36.4% castor oil. The polycarbophil dose regimens evaluated were 1, 1.5, 2, or 3 gm at 30-min intervals after castor oil to total the usual prescribed dose of 6 gm/day. One gram taken every 30 min for six doses lowered the number of bowel movements and also induced the least number of cramps and lowest cramp severity rating (reported by subjects). The same total dose over a different dosing interval was no more effective than placebo. Clinical Pharmacology and Therapeutics (1982) 31, 766–769; doi:10.1038/clpt.1982.108
To evaluate the response during insulin-induced hypoglycemia, diabetics treated with relatively selective or nonselective beta-adrenergic blocking agents were studied. Placebo, atenolol (100 mg/day), and propranolol (80 mg b.i.d.) were administered to 12 insulin-treated diabetics for 1 week in a double-blind, randomized, crossover fashion with a 2-week washout between treatments. Sufficient intravenous insulin (0.2-0.6 units/kg) was administered to decrease plasma glucose 68% from the basal level or to less than 60 mg/dl within 90 minutes. Blood pressure changes at the nadir of plasma glucose were +15.2/-9.9 mm Hg for placebo, +27.9/0 mm Hg for atenolol, and +38.8/+14.3 mm Hg for propranolol. Diastolic blood pressure changes induced by propranolol were significantly different from those induced by atenolol (p less than 0.01) and placebo (p less than 0.01), and systolic pressure changes were significantly different (p less than 0.02) between propranolol and atenolol. Mild seizures developed in two patients treated with propranolol. Their blood pressure changes at the plasma glucose nadir were +56/+22 and +86/+31 mm Hg. Other symptoms of hypoglycemia were more frequent during beta-blocker than during placebo treatment. Differences in response may be related to the relatively selective adrenergic blocking effect of these drugs.
This double-blind, randomized, parallel, placebo-controlled study evaluated the analgesic effects of single oral doses of 30 mg nalbuphine, 650 mg acetaminophen, and the contribution of each to the efficacy of their combination in 128 hospitalized patients with postoperative pain. Subjective reports of patients evaluated each hour for 6 hours were used as indices of analgesic response. Both nalbuphine and acetaminophen were significantly superior to placebo for most measures of total and peak analgesia. The interaction contrast between nalbuphine and acetaminophen was not significant for any analgesic measurements, indicating an additive effect of the components. The combination was the most effective treatment, followed by nalbuphine, acetaminophen, and placebo. Effects of the combination were significantly different from those of acetaminophen at 4, 5, and 6 hours and from those of placebo at 1 to 6 hours. There was no significant difference in the frequency or intensity of side effects among the groups. The combination of nalbuphine and acetaminophen appears to be a therapeutically useful combination. Clinical Pharmacology and Therapeutics (1986) 39, 295–299; doi:10.1038/clpt.1986.42
