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Biomedical subjects

W W Offen

Publications and source records attributed to W W Offen.

29 records · Page 2Linked to original sources
PubMed1988

Pharmacokinetics and pharmacodynamics of oral nizatidine.

Nizatidine was studied in six high-acid-secretor (basal secretion, greater than or equal to 5 mEq/hr) male volunteers in a randomized, double-blind, nonbalanced, cross-over, placebo and standard drug-controlled study. Doses of 75 mg, 150 mg, and 300 mg bid were compared with placebo and cimetidine 300 mg qid. Nocturnal acid output was significantly reduced (P less than .01) by all doses of nizatidine (36 +/- 22, 36 +/- 31, and 26 +/- 20 mEq) with 75 mg, 150 mg and 300 mg, respectively, and also by cimetidine (43 +/- 39 mEq) as compared with placebo (101 +/- 61 mEq). Nizatidine also significantly reduced meal-stimulated acid secretion at breakfast (14 +/- 9, 9 +/- 7, and 5 +/- 6 mEq/2 hours with 75 mg, 150 mg, and 300 mg, respectively, P less than .01), at lunch (50 +/- 22, 57 +/- 22 and 50 +/- 35 mEq/2 hours, P less than .05) but did not have any effect at dinner (65 +/- 16, 78 +/- 24, and 71 +/- 17 mEq/2 hours) whereas cimetidine, given every 6 hours, significantly (P less than .01) reduced meal-stimulated acid secretion (25 +/- 16, 27 +/- 20 and 31 +/- 15 mEq/2 hours, breakfast, lunch, and dinner, respectively) as compared with placebo (81 +/- 30, 76 +/- 25, and 66 +/- 16 mEq/2 hours, breakfast, lunch, and dinner, respectively). Both drugs have a similar pharmacokinetic profile. Nizatidine seems to be a promising H2 antagonist, more potent than cimetidine (on an mg/mg basis), and efficacy studies on gastric acid disorders should be performed.

Administration, Oral↗
PubMed1988

Pinacidil with and without hydrochlorothiazide. Dose-response relationships from results of a 4 x 3 factorial design study.

Utilising a modified fixed-dose, 4 x 3 factorial design, the antihypertensive effects of all combinations of 4 doses of pinacidil (0, 12.5, 25 and 37.5 mg bid) with 3 doses of hydrochlorothiazide (0, 12.5 and 25 mg bid) were studied in patients with supine diastolic blood pressure of 95 to 110mm Hg. The decreases in supine diastolic blood pressure from baseline were dose-related for both drugs. The response to the highest monotherapy dose of pinacidil was less in patients with oedema. When given in combination, hydrochlorothiazide blunted the differences among pinacidil doses so that 12.5 mg pinacidil with 12.5mg hydrochlorothiazide administered twice daily produced nearly maximal antihypertensive efficacy. For pinacidil monotherapy, the incidence of oedema was 3%, 26% and 47% at dosages of 12.5, 25, and 37.5mg bid, respectively, with significant attenuation of these effects at both hydrochlorothiazide dosage levels. Based upon these data, low (12.5-25mg bid) doses of pinacidil are effective and safe as monotherapy for hypertension. The optimal combination of pinacidil with hydrochlorothiazide given twice daily for hypertension contains 12.5mg of each drug.

Antihypertensive Agents↗
PubMed1988

Effect of nizatidine and cimetidine on betazole-stimulated gastric secretion of normal subjects: comparison of effects on acid, water, and pepsin.

The effect of nizatidine, a new histamine H2 receptor antagonist, on gastric secretory function of eight normal subjects stimulated with betazole, was compared with that of cimetidine. Single oral doses of 75 mg, 150 mg, and 300 mg nizatidine, 300 mg cimetidine, and a placebo were administered on separate occasions 1 h before betazole stimulation. Gastric secretions were recovered in 15-min fractions for the ensuing 2 h, and the pH, H+ concentration and output, volume, and pepsin concentration and output were determined. Doses of 150 mg and 300 mg nizatidine depressed the secretory response significantly more than did cimetidine. The antisecretory effects of 75 mg nizatidine was no different than that of 300 mg cimetidine. Nizatidine 300 mg inhibited pepsin output significantly more than volume. Although pepsin concentration was reduced more than volume, the difference was not significant. These observations, in contrast to results of previous studies, suggest a direct inhibition of pepsin secretion, although to a lesser extent than that of acid.

Adult↗
PubMed1987

Enteric coating of fenoprofen calcium reduces gastrointestinal microbleeding.

The effects of plain and enteric-coated fenoprofen calcium (Nalfon, Dista, Indianapolis, Ind.) on gastrointestinal microbleeding were studied in 32 normal male volunteers in a randomized, open-label, parallel trial at two inpatient research facilities. A 1-week placebo (baseline) period preceded 2 weeks of fenoprofen therapy (enteric coated or plain, 600 mg q.i.d.). Fecal blood loss was measured by 51Cr-tagged erythrocyte assay and averaged over days 4 to 7 (baseline) and 11 to 14 and 18 to 21 (active therapy). At one center gastrointestinal irritation was evaluated endoscopically before and after active therapy. Endoscopy showed both formulations to cause mucosal damage not evident by subject-reported symptoms. Four of the 16 subjects developed asymptomatic duodenal ulcers. Mean daily fecal blood loss was significantly lower (P = 0.03) with enteric-coated (mean +/- SD, 1.104 +/- 0.961 ml/day) than with plain fenoprofen calcium (mean +/- SD, 1.686 +/- 0.858 ml/day), suggesting that tolerance of fenoprofen can be improved with administration in an enteric-coated form.

Adult↗
PubMed1987

A pharmacokinetic profile of nizatidine in man.

In this report, the pharmacokinetic, pharmacodynamic, and hormonal effects of nizatidine are reviewed in healthy volunteers and in patients with renal or hepatic impairment. The absolute oral bioavailability of nizatidine exceeded 90%; the half-life (t1/2), plasma clearance (Clp), and volume of distribution (Vd) of iv nizatidine were 1.3 h, 461/h, and 1.21/kg, respectively. Within 16 h of dosing volunteers with nizatidine, more than 90% of the administered dose was recovered in urine as parent drug and metabolites; unchanged nizatidine accounted for 65 and 75% of the recovered substances, after oral and intravenous administration, respectively. Renal impairment decreased the elimination of nizatidine and dosage reductions are recommended for patients with creatinine clearance (Clcr) less than 50 ml/min/m2. Nizatidine suppressed gastric acid secretion produced by sham meals, protein meals, or pentagastrin; its antisecretory activity was dose and concentration dependent. Nizatidine was three times more potent than cimetidine. Nizatidine, after oral or iv administration, did not alter hormone concentrations in plasma.

Adult↗
PubMed1987

Treatment of duodenal ulceration in the United States.

Nizatidine, a new H2-receptor antagonist for the treatment of duodenal ulcer disease, was compared with placebo in a dose-response, double-blind, parallel, multicenter clinical trial. Patients were randomly allocated to receive either nizatidine (25 mg b.i.d., 150 mg b.i.d., or 300 mg at bedtime) or placebo. At the end of 4 weeks, patients whose ulcer had not healed were randomly reallocated to receive either the nizatidine 150 mg b.i.d. dosage regime or placebo for an additional 4 weeks. Nizatidine doses of 300 mg at bedtime and 150 mg b.i.d. demonstrated similar healing frequencies. Both of these doses were statistically significantly superior in ulcer healing to the nizatidine 25 mg b.i.d. dose and to placebo at the end of 4 weeks. Patients randomly reallocated to receive nizatidine had significantly greater healing rates than patients randomly reallocated to receive placebo. In summary, nizatidine given as a single evening dose of 300 mg or as 150 mg b.i.d. proved to be equally safe and effective in the healing of active duodenal ulcers.

Adult↗
PubMed1987

Nizatidine as maintenance therapy of duodenal ulcer disease in remission.

A new H2-receptor antagonist, nizatidine (150 mg h.s.), was compared with placebo as maintenance therapy in a randomized, parallel, double-blind, one-year study of 513 patients with recently healed duodenal ulcer. Endoscopies were performed at 0, 3, 6, and 12 months and at unscheduled times if symptoms of active peptic ulcer disease were present. Cumulative ulcer recurrence rates for nizatidine and placebo were 13 versus 40% at 3 months, 24 versus 57% at 6 months, and 34 versus 64% at 12 months. The differences were significant (p less than 0.001) at each treatment period. Smokers in both treatment groups had significantly greater recurrence rates than non-smokers. Symptoms of peptic ulcer disease were significantly less in nizatidine-treated patients in the first 3 months of treatment. Adverse events, including those related to peptic ulcer disease, occurred more frequently in placebo-treated patients. Nizatidine proved to be safe and effective in preventing recurrences of duodenal ulcer.

Clinical Trials as Topic↗
PubMed1985

Intravenous nizatidine kinetics and acid suppression.

The effectiveness of intravenous nizatidine in suppressing gastric acid secretion was evaluated by different methods of inducing secretion in two single-blind studies. In study 1, seven subjects were given single, 20-min intravenous infusions of nizatidine (6.25, 25, 75, 150, or 250 mg) before modified sham feeding (MSF). Gastric acid suppression after nizatidine was contrasted with that after placebo and MSF. All doses of nizatidine reduced secretion; the 150- and 250-mg doses of nizatidine suppressed secretion for at least 2.5 hr. In study 2, eight subjects received one 5-min intravenous infusion of placebo, cimetidine (300 mg), or nizatidine (25, 50, 100, or 250 mg) weekly for 6 wk. Secretion was induced by infusing pentagastrin (2 micrograms/kg/hr) 45 min before the study drug was dosed and for 3.5 hr thereafter. Again, all doses of nizatidine reduced gastric acid, chiefly by decreasing volume. Nizatidine induced a clear dose-response effect; nizatidine (100 mg) and cimetidine (300 mg) had approximately equal suppressive effects. Nizatidine (100 mg) and cimetidine (300 mg) reduced acid output by 62% and 63% and reduced volume of secretion by 48% and 51% over the 3.5-hr period. Gastric acid suppression and plasma nizatidine concentrations were directly related. Nizatidine kinetics were linear and proportional to dose. The t1/2 was 1.3 hr (range 0.7 to 2.1 hr), the volume of distribution was 1.2 +/- 0.5 l/kg, and clearance was 0.6 +/- 0.2 l/kg/hr. Laboratory abnormalities and side effects were minor in both studies.

Adult↗
PubMed1985

Dose response to fenoprofen calcium using placebo and codeine as controls.

This paper evaluates the dose-response relationship of several doses of fenoprofen calcium, between 12.5 and 300 mg, and their relationship to 60 mg of codeine sulfate and placebo. Three separate parallel studies are included in this evaluation, including a total of 867 patients. The types of pain were cesarean section, episiotomy wound, uterine cramping, and general surgery. This paper shows that a significant increasing relationship exists between efficacy and dose of fenoprofen, suggesting that relatively larger doses of fenoprofen will achieve greater amounts of efficacy.

Cesarean Section↗
PubMed1982

A double-blind study comparing benoxaprofen, aspirin, and benoxaprofen plus aspirin in patients with rheumatoid arthritis.

Ten patients with rheumatoid arthritis completed a study that consisted of 30-day treatment periods with aspirin, benoxaprofen, and benoxaprofen plus aspirin. There were two-week placebo washouts between each treatment. The patients were evaluated biweekly for 15 variables. Each variable was compared for each period; a pooled index was calculated on three combinations of variables. The benoxaprofen-plus-aspirin combination was significantly better than aspirin and better than benoxaprofen alone. This study indicates that combining nonsteroidal anti-inflammatory drugs which inhibit different sites of the inflammatory response (i.e., benoxaprofen, an inhibitor of the directional migration of monocytes, with aspirin, a potent inhibitor of prostaglandin synthesis) may be advantageous in treating patients with rheumatoid arthritis.

Adult↗