PubMed Health⌕ Search

Biomedical subjects

N R Cutler

Publications and source records attributed to N R Cutler.

18 recordsLinked to original sources
PubMed1992

A dose-response trial of once-daily diltiazem.

This trial was performed to determine the safe and effective dosage range of once daily diltiazem (diltiazem CD) capsules for treatment of essential hypertension. Patients with essential hypertension having supine diastolic blood pressure values greater than or equal to 95 mm Hg and less than or equal to 110 mm Hg were randomly assigned to receive placebo or one of four doses of diltiazem CD: 90, 180, 360, or 540 mg. Blood pressure was measured at trough, 24 hours after the dose, and at the time of peak effect, 10 hours after the dose. Diltiazem CD lowered both supine diastolic and systolic blood pressure. A linear dose response was seen with changes in diastolic and systolic blood pressure and heart rate for trough and peak measurements. Trough/peak ratios for the 180, 360, and 540 mg doses were all greater than 0.50. Adverse effects were dose related; those most commonly reported were headache (8.6%), bradycardia (8.1%), and edema (7%), with bradycardia and edema possibly dose related. It is therefore concluded that diltiazem CD is a safe and effective antihypertensive agent.

Adolescent↗
PubMed1992

A comparison of circulating hormone levels in postmenopausal women receiving hormone replacement therapy.

Seventeen postmenopausal subjects were randomized into this comparative study of esterified estrogen 0.625 mg (Estratab), esterified estrogen 0.625 mg plus 1.25 mg methyltestosterone (Estratest H.S.), or conjugated estrogen 0.625 mg (Premarin). Sixteen subjects completed the study in which plasma hormone concentrations of estrone and estradiol were assessed at various time points. There were no significant differences among the treatment groups.

Adult↗
PubMed1992

Detection of benzodiazepines in human hair by radioimmunoassay.

OBJECTIVE: In this preliminary investigation, we sought to determine whether a standard benzodiazepine radioimmunoassay (RIA) could detect three benzodiazepines in human hair. DESIGN: Hair samples of 20-50 strands (minimum 10 mg) were cut from eight patients receiving diazepam, two patients receiving alprazolam, three patients receiving lorazepam, and two negative controls. Samples were treated with ethanol and phosphate buffer washes at 37 degrees C to remove external contamination. The protein hair matrix was destroyed using proprietary procedures, then analyzed with Abuscreen RIA designed to detect various benzodiazepines and their metabolites, using oxazepam as a reference standard. SETTING: Patients were hospitalized in a locked psychiatric facility. PATIENTS: Twelve patients with chronic psychiatric conditions who had received therapeutic dosages of benzodiazepines for 1-11 months were included in the sample. One outpatient who reported heavy prior diazepam use was also included. MAIN OUTCOME MEASURE: Detection of benzodiazepines was well above a 1.5 ng/10 mg cutoff level with the Abuscreen assay. RESULTS: Diazepam was readily detected, but alprazolam and lorazepam were not detected. CONCLUSIONS: There is no test that can currently determine duration and extent of prior benzodiazepine use. Hair analysis for diazepam offers a potential, new clinical and research tool for characterizing prior level and extent of usage.

Adult↗
PubMed1992

Implications of the study population in the early evaluation of anticholinesterase inhibitors for Alzheimer's disease.

OBJECTIVE: Velnacrine testing for tolerance and safety in both normal elderly subjects and patients with Alzheimer's disease (AD) is reviewed to illustrate the importance of Phase I trials in the target group as more predictive of safety and tolerance for subsequent multicenter trials than those conducted in healthy elderly subjects. DESIGN: Both a single-dose and a randomized, double-blind, placebo-controlled, ascending, multiple-dose study were performed with healthy, elderly men. In the multiple-dose study, the subjects were randomized to four groups of 14, with 10 subjects receiving velnacrine and 4 receiving placebo. The doses were velnacrine 25 (group 1), 50 (group 2), and 100 mg (group 3), respectively, administered twice daily; group 4 received 100 mg three times daily for 28 days. Blood and urine were collected serially for the pharmacokinetic assessment. With AD patients, 24 subjects were randomly assigned to receive either placebo or velnacrine for 10 days in a double-blind, sequential escalation study in a hospital setting. There were three groups of 8 subjects. Six patients in each group received velnacrine and 2 placebo. The three groups received respective dosages of 450, 300, and 225 mg/d three times daily. Adverse events were closely monitored and recorded. PATIENTS/PARTICIPANTS: The multiple-dose test in healthy elderly men included 56 men, aged 60-74 years. Rigorous screening for any potential complications that could affect absorption, distribution, metabolism, or excretion preceded patient entry in the AD patient study. Patients with a history of major psychiatric, neurologic, and cardiovascular disorders were excluded. The patients ranged in age from 56 to 89 years, and were equally distributed between gender. INTERVENTION: Velnacrine was administered in various doses. MAIN OUTCOME MEASURES: We emphasize the extreme adverse effects encountered in the AD patient group compared with the healthy group. Plasma concentrations of velnacrine over time in both groups are given, as well as the drug's half-life and excretion rates. RESULTS: The tolerable dosage predicted by studies performed in healthy elderly subjects was 300 mg/d. This dosage was not tolerable among the AD patients. A dosage as high as 450 mg/d resulted in a tonic seizure in one patient. The predicted dosage of 300 mg/d produced an adverse effect profile in AD patients that included dizziness, nausea and/or vomiting, headaches, and severe diarrhea. AD patients tolerated a dosage of 225 mg/d. CONCLUSIONS: A velnacrine dosage of 300 mg/d that was tolerated in healthy elderly subjects was not tolerated by AD patients.

Aged↗
PubMed1992

Pharmacokinetics and dose proportionality of D2-agonist MK-458 (HPMC) in parkinsonism.

To investigate the pharmacokinetic profile, bioavailability, and dose proportionality of the D2-agonist MK-458 (hydroxypropylmethylcellulose tablet, a sustained release formulation), a 4-period crossover study was conducted in 10 patients with mild to moderate Parkinson's disease (mean age = 63 y; 1 woman, 9 men). Following a titration phase to induce tolerance, each patient was given single oral doses of 6, 12 and 18 mg and a single intravenous 40 micrograms dose (5 micrograms/h over 8h). The maximum concentrations of MK-458 observed in plasma after oral administration were 139, 240 and 344 ng/L for the 6, 12 and 18 mg doses, respectively, and occurred after 8.0, 9.0 and 5.5 h, respectively. Mean areas under the plasma concentration-time curves were 1728, 2849 and 5484 ng/L.h, respectively. The mean plasma half-life was 3.8 h and mean plasma clearance was 3390 ml/min (203.4 L/h). The bioavailability (approximately 5%) was very similar for the 3 tablet formulations tested. The disposition of MK-458 was independent of the dose over the range of doses studied.

Administration, Oral↗
PubMed1978

The tricyclic antidepressants.

Because only 9.4% of depressions are recognized at initial evaluation by primary physicians, the diagnosis of depression is important. Forty percent of a group of mixed depressions will resolve in a month without treatment, and 70% will resolve with the use of tricyclic antidepressants. Research on plasma levels of tricyclic antidepressants suggest new clinical strategies for adjusting dosages; neurochemical studies may provide an appropriate selection process for choosing a tricyclic antidepressant.

Antidepressive Agents, Tricyclic↗
PubMed1978

Who was first?

Explore the source record for details and available documents.

Authorship↗
PubMedDate not supplied

Alzheimer's patients should be included in phase I clinical trials to evaluate compounds for Alzheimer's disease.

Dosage and tolerance are critical issues in successful drug therapy for patients with Alzheimer's disease (AD). A clear distinction among patient populations and AD patient subpopulations is necessary to ensure a thorough assessment of new central nervous system-active compounds. Phase I inpatient trials, in which tolerance and safety are evaluated under double-blind conditions in the target population, provide valuable information for use in planning multicenter outpatient trials. In similar studies, even those involving the elderly, tolerance and safety outcomes in healthy volunteers are not always predictable. An early trial of the effects of velnacrine in healthy, elderly, male volunteers was followed by a trial in the target population. A group of volunteers, aged 60 to 74 years who did not have AD, received 300 mg of velnacrine each day. This dosage was well tolerated for 28 days. Diarrhea, generally of moderate severity, was the only reported adverse effect. No subjects were required to discontinue taking velnacrine. In contrast, a similar trial showed a dosage of 300 mg of velnacrine each day intolerable among patients with AD. Adverse reactions to dosages greater than 225 mg/day included dizziness, fainting, nausea and/or vomiting, headache, and severe diarrhea. A velnacrine dosage of 225 mg/day appeared to be safe and well tolerated in a small population of healthy patients with AD. Based on the inpatient experience with AD subjects, a maximum dose of 225 mg/day was adopted for outpatient studies. Although factors that may contribute to drug sensitivity in patients with AD vary beyond conclusive parameters, the observed sensitivity within the target AD group may indicate a safety/tolerance study as a worthwhile antecedent to multicenter efficacy trials.

Administration, Oral↗