Biomedical subjects
C R Benedict
Publications and source records attributed to C R Benedict.
Safe and effective management of hypertension with fixed-dose combination therapy: focus on losartan plus hydrochlorothiazide.
Treatment of hypertensive patients with fixed-dose combination therapy consisting of losartan and hydrochlorothiazide (HCTZ) has several potential benefits over monotherapy with each of the individual components: more effective blood pressure control, a reduction in the likelihood of adverse effects, and facilitation of patients staying on therapy due to a simple once-daily regimen. Losartan plus HCTZ fixed-dose combination therapy lowers blood pressure in mild to moderate or severe hypertensive patients to a level comparable with other classes of antihypertensive drugs in combination with HCTZ. Fixed-dose combination therapy with losartan plus HCTZ is therefore an excellent choice for hypertensive patients in whom combination therapy is necessary to achieve additional blood pressure reductions.
Single-dose, placebo-controlled, phase I study of oral dolasetron.
STUDY OBJECTIVES: To evaluate the safety, tolerability, and pharmacokinetics of single, escalating doses of oral dolasetron mesylate, a new 5-HT3 receptor antagonist. DESIGN: Double-blind, placebo-controlled, dose-escalating phase I study. SETTING: A clinical research center. PATIENTS: One hundred twenty healthy male volunteers. INTERVENTIONS: Subjects received either placebo or oral dolasetron mesylate 50, 100, 150, 200, 250, 300, or 400 mg. MEASUREMENTS AND MAIN RESULTS: Compared with placebo, subjects receiving dolasetron mesylate reported a greater frequency of headache, light-headedness, dizziness, increased appetite, and nausea. There were no clinically significant changes in mean laboratory values from before to after treatment. Adverse events were transient, mild or moderate, and similar to those after single intravenous doses of the drug. No clinically significant electrocardiographic changes occurred, but lengthening of the QRS complex duration and dose-dependent lengthening of PR and QTc intervals were observed 1-2 hours after dosing. These effects were asymptomatic and were mainly associated with higher doses (< or = 300 mg). CONCLUSION: Dolasetron mesylate is well tolerated when administered in single oral doses up to 400 mg to healthy volunteers. Clinical trials are under way to evaluate the agent's efficacy in preventing chemotherapy-induced and postoperative nausea and vomiting with doses up to 200 mg.
Multiple-dose, placebo-controlled, phase I study of oral dolasetron.
STUDY OBJECTIVES: To evaluate the safety, tolerability, and pharmacokinetics of increasing dose levels of oral dolasetron mesylate, a new 5-HT3 antagonist. DESIGN: Double-blind, placebo-controlled, dose-ranging phase I study. SETTING: A clinical research center. PATIENTS: Forty healthy male volunteers. INTERVENTIONS: Eight subjects at each dose level were randomized in a ratio of 3:1 to receive either dolasetron mesylate 25, 50, 100, 150, or 200 mg in a single oral dose on days 1 and 9, and twice/day on days 2-8, or placebo for 9 days. MEASUREMENTS AND MAIN RESULTS: Dolasetron was well tolerated at all dose levels. The adverse event rates for dolasetron- and placebo-treated subjects who experienced at least one adverse event were 80% and 50%, respectively. Most frequently reported by subjects receiving dolasetron were headache, constipation, flatulence, and lightheadedness. They generally were mild, and none was severe. No dose-response relationship was apparent for any adverse event. There were no clinically significant changes in mean laboratory values or vital signs. Asymptomatic treatment-related electrocardiographic changes were consistent with the drug's electrophysiologic properties. These changes have been well characterized and have thus far been clinically unimportant. Pharmacokinetics of the reduced metabolite were dose independent, and multiple-dose exposure of this metabolite can be predicted from its single-dose values. CONCLUSION: Oral dolasetron mesylate was well tolerated when administered in doses up to 200 mg/day for 9 days in healthy volunteers.
Oral dolasetron mesylate in patients receiving moderately emetogenic platinum-containing chemotherapy. Oral Dolasetron Dose Response Study Group.
PURPOSE: This double-blind, dose-response study was conducted to assess the safety and efficacy of four oral doses of dolasetron mesylate for preventing acute emesis in cancer patients receiving their first course of moderately emetogenic platinum-containing chemotherapy. PATIENTS AND METHODS: Patients were randomized to receive a single oral dose of 25, 50, 100, or 200 mg dolasetron 30 minutes before receiving IV carboplatin (275-400 mg/m2)- or cisplatin (20-50 mg/m2)-containing chemotherapy, then monitored for nausea and vomiting for 24 hours. RESULTS: Three hundred seven cancer patients from 32 sites completed the study. There was a statistically significant dose response across the four doses for complete response (no emetic episodes or rescue medication): 44.7%, 71.3%, 73.2%, and 82.5% for the 25, 50, 100, or 200 mg doses of dolasetron, respectively. Patients' nausea severity and patient satisfaction visual analogue scale scores also showed a statistically significant trend with dose. All doses of dolasetron were well tolerated. The most common adverse events were headache (17.6%) and dizziness (2.0%). DISCUSSION: This study demonstrates the safety and antiemetic efficacy of oral dolasetron mesylate in patients receiving moderately emetogenic platinum-containing chemotherapy with the highest antiemetic activity observed at 200 mg.