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Biomedical subjects

D J Weidler

Publications and source records attributed to D J Weidler.

At least 37 records · Page 2Linked to original sources
PubMed1989

Predicting home and work blood pressure measurements from resting baselines and laboratory reactivity in black and white Americans.

The relationship between blood pressure in the laboratory (both at rest and in response to laboratory tasks) and ambulatory blood pressure at home and at work was evaluated. One hundred nineteen normotensive and unmedicated mild-moderate hypertensive black and white females and males participated in laboratory blood pressure monitoring at rest and during four challenging tasks (structured interview, video game, bicycle exercise, and cold pressor test) as well as ambulatory blood pressure monitoring while at home and at work. Baseline blood pressure taken while subjects were at rest was the strongest predictor of ambulatory systolic blood pressure (r = .64) and diastolic blood pressure (r = .77) at work. Among reactivity tasks the strongest predictors of ambulatory blood pressure in the total population were the structured interview and the video game (both psychological tasks) followed by the cold pressor test. Racial comparisons, however, determined that the cold pressor test predicted diastolic blood pressure significantly better for blacks (r = .73) than for whites (r = .40), suggesting a possible difference in blood pressure regulation.

Adult↗
PubMed1988

Fluconazole penetration into cerebrospinal fluid in humans.

One hour after intravenous doses of 50 mg/d fluconazole for 6 days or 100 mg/d for seven days to healthy subjects, the cerebrospinal fluid concentrations of fluconazole were 1.26 mg/L and 2.74 mg/L, respectively. These values were approximately 52% and 62% those of serum. Four patients with an initial clinical diagnosis of meningitis also had significant concentrations of fluconazole in the cerebrospinal fluid.

Fluconazole↗
PubMed1988

Cardioselectivity of cetamolol compared with atenolol and nadolol.

The selectivity of the beta-adrenoceptor blockade produced by single oral doses of cetamolol, atenolol, and nadolol was compared in normal male subjects. Study 1 established the dose at which each drug provides equivalent beta-1 blockade. Beta-1 blockade was estimated using the degree of inhibition of the increased heart rate (HR) response to graded exercise. Cetamolol (30 mg), atenolol (100 mg), and nadolol (80 mg) all attenuated the HR response to a comparable extent. This result established that the dose ratio of cetamolol:atenolol:nadolol of 1.00:3.33:2.67 provides equipotent beta-1 blockade. This ratio of doses was used in Studies 2 and 3 to evaluate the antagonism of beta-2-mediated responses to titrated doses of intravenous isoproterenol (ISO) by low and high doses of each drug. Beta-2 blockade was assessed using the attenuation of ISO-induced reductions in diastolic blood pressure (DBP) in Study 2 and ISO-induced increases in specific airway conductance (sGAW) in Study 3. For within drug comparisons, antagonism of the HR increase induced by ISO (a response mediated by both beta-1 and beta-2 receptors) was also examined. Treatments included cetamolol (15 and 60 mg), atenolol (50 and 200 mg), and nadolol (40 and 160 mg in Study 2; 40 mg only in Study 3). All drugs tested suppressed the HR, DBP, and sGAW responses to ISO, and this blockade was dose dependent. Cetamolol and nadolol produced approximately equipotent beta-1 blockade, whereas cetamolol at both doses produced a less potent beta-2 blockade. Atenolol antagonized ISO effects on all parameters less than either cetamolol or nadolol. Quantitative cardioselectivity indices revealed that cetamolol 60 mg was the most cardioselective and nadolol 40 mg the least. Data from the three studies demonstrate that cetamolol is cardioselective relative to nadolol and that, in contrast to atenolol, cardioselectivity appears to increase at the higher dose.

Acetamides↗
PubMed1988

Efficacy and pharmacokinetics of oral pirmenol, a new antiarrhythmic drug.

Pirmenol is a new orally effective antiarrhythmic agent. Reported are the results of oral administration of pirmenol to six patients (age 48.5 +/- 8.6 years, weight 83 +/- 15 kg) with stable ventricular extrasystoles (PVCs)--average ectopy rate 1040 +/- 630/hr (mean +/- SD). Patients received oral doses of placebo or 200 mg of pirmenol in a double-blind cross-over fashion followed by a single-blind rising-dose administration of 250 mg and 300 mg of pirmenol. The time period between doses was 48 hours. Pirmenol was rapidly absorbed (time to peak plasma levels 1 to 1.5 hours) and the mean maximum plasma concentrations were 1.8, 2.7 and 3.4 micrograms/mL with 200-mg, 250-mg and 300-mg doses, respectively. The elimination half-life was 9.3 +/- 3.0 hours and 31 +/- 14% of the dose was recovered in urine. The response criterion (80% suppression of PVCs of control for 8 hours) was met after the 300-mg dose in three patients. In three patients greater than 80% reduction occurred for up to 8 hours after the 200-mg dose. Pirmenol administration was not associated with any significant changes in blood pressure, heart rate, hepatic and renal function, PR interval or QRS duration. LV ejection fraction determined echocardiographically decreased from 63.0 +/- 6.9% predose to 59.7 +/- 5.0% about 2 hours after the 300-mg dose and QT interval increased by less than 10%. Two patients complained of transient bad taste sensation. Our results suggest that 250 mg to 300 mg of pirmenol, administered twice a day will suppress the PVCs effectively.

Administration, Oral↗
PubMed1988

Low-dose acebutolol given once daily in the treatment of chronic angina pectoris.

Acebutolol, a beta-1 selective beta blocker with intrinsic sympathomimetic activity has been shown to be an effective agent in chronic angina pectoris therapy, with twice or three times daily dosing. The long-term effects of 400 mg of acebutolol given only once a day versus placebo on exercise hemodynamics, ST segment depression, and rate pressure product were studied. Eleven patients (mean age, 60 +/- 12 years) with hypertension and chronic angina pectoris were enrolled. Resting heart rate was not significantly altered after therapy, (80 vs 72 bpm). Objective measurements from exercise treadmill tests showed significant reduction in peak heart rate from 130 to 103 bpm, systolic blood pressure from 197 to 167 mm Hg, rate pressure product (from 25 to 18 bpm-mm Hg X 1000), and ST depression in patients receiving acebutolol compared with those receiving placebo. No significant adverse effects were reported. These data indicate that acebutolol may be efficacious as once daily therapy for chronic stable angina pectoris.

Acebutolol↗
PubMed1988

Blood pressure stability of normotensives and mild hypertensives in different settings.

Generalizability theory was used to examine the stability of blood pressure (BP) measurement in normotensives and mild hypertensives. Three to six readings at home or at work provided adequate reliability for the same day in each setting. Under structured laboratory conditions, two to three BP measures taken on each of 2 to 3 days for systolic and diastolic BP provided conservative estimates that were generalizable across days. Finally, generalizations across settings called for five or more measurements taken in at least two settings.

Adult↗
PubMed1988

Pharmacokinetics of thiopental in the asphyxiated neonate.

The pharmacokinetic properties of thiopental were studied in 10 asphyxiated neonates (mean +/- SE; birth weight, 3,244 +/- 212 g; gestational age, 40 +/- 1 weeks) as part of a randomized, controlled trial which tested the ability of barbiturate therapy to decrease central nervous system damage secondary to perinatal asphyxia. Therapy was begun at a mean age of 2.3 h in all and was initially given as a loading dose of 15 mg/kg over 30 min followed by a constant infusion. The mean steady-state thiopental concentration was 13.4 +/- 3.7 micrograms/ml (mean +/- SD) and the average time to reach steady state was 7 +/- 5 h. Mean elimination half-life, plasma clearance and volume of distribution for thiopental were 39 h (range 26-70), 66 ml/(h x kg) (range 31-172), and 3.6 liters/kg (range 1.1-6.7), respectively. Arterial blood pressure support was required in 8 of 10 patients. While it appears feasible to give thiopental to the asphyxiated neonate at the reported infusion rates, the risk-benefit ratio is increased by the frequent associated hypotension and need for pharmacologic blood pressure support.

Asphyxia Neonatorum↗
PubMed1988

Verapamil vs quinine in recumbent nocturnal leg cramps in the elderly.

In an open-labeled trial with eight elderly patients (aged 62 to 87 years) suffering from nocturnal leg cramps refractory to treatment with quinine sulfate, we ruled out other active disease processes and substituted verapamil hydrochloride therapy (120 mg at bedtime). Response to treatment was assessed by biweekly observations by the primary care physician and nightly by the research registered nurse for the entire duration of the trial, lasting eight weeks. Observations made and clinical conditions reported were indicative of improvement and disappearance of cramping when therapy was changed from quinine to verapamil. This noteworthy improvement in patients with recumbent nocturnal leg cramps is an important finding and merits further investigation.

Aged↗
PubMed1987

A double-blind parallel trial to assess the efficacy of doxazosin, atenolol and placebo in patients with mild to moderate systemic hypertension.

The antihypertensive and lipid effects of doxazosin and atenolol were compared in a 10-week, double-blind, parallel, placebo-controlled study. The 129 adults enrolled had mild to moderate hypertension (average supine diastolic blood pressures for doxazosin, atenolol and placebo were 100.6, 101.0 and 99.7 mm Hg, respectively). Patients were randomly assigned to treatment with doxazosin, 1 to 16 mg daily, atenolol, 50 to 100 mg daily or placebo. Among 114 patients included in the efficacy analysis, standing blood pressure (systolic/diastolic) changed by -13/-11 mm Hg with doxazosin (n = 37), -12/-12 mm Hg with atenolol (n = 39) and +1/-1 mm Hg with placebo (n = 38). Mean reductions in blood pressure for doxazosin and atenolol were significantly greater than those for placebo (p less than 0.01), although no statistically significant differences between the active agents were noted. Serum lipid measurements were evaluable for 116 patients, and the 38 doxazosin-treated patients in this group experienced reductions in total cholesterol, total triglyceride and very low density lipoprotein cholesterol levels. Both doxazosin and atenolol demonstrated comparable acceptance profiles. Doxazosin is an effective hypotensive agent with beneficial effects on serum lipid levels.

Adrenergic alpha-Antagonists↗
PubMed1987

A multiple-dose pharmacokinetic comparison of naproxen as a once-daily controlled-release tablet and a twice-daily conventional tablet.

The bioequivalence and absorption kinetics of naproxen in a new controlled-release tablet (750 mg or 1,000 mg naproxen) administered once daily were determined relative to an equivalent dose of the conventional naproxen tablet (375 mg or 500 mg naproxen) administered q12h. Naproxen was well absorbed from the controlled-release tablet (about 90%) compared with the conventional tablet. Absorption was dependent on drug release from the tablet matrix. The mean absorption time of naproxen averaged 8.4 hours for the 750-mg controlled-release tablet and 9.2 hours for the 1,000-mg controlled-release tablet. Once-daily administration of the controlled-release tablet resulted in equivalent trough concentrations of naproxen, and steady-state plasma concentrations were maintained within narrower limits than with twice-daily naproxen.

Adult↗
PubMed1987

Pharmacokinetics and pharmacodynamics of long-acting propranolol 60-mg capsules: a comparative evaluation.

This double-blind, placebo-controlled, four-period cross-over study was undertaken to evaluate the sustained-release characteristics of long-acting propranolol hydrochloride (Inderal LA, Ayerst Laboratories, New York, NY) 60 mg qd, to compare the pharmacokinetic and pharmacodynamic properties of this formulation with conventional propranolol 20 mg tid, and to evaluate the proportionality of long-acting propranolol 60 mg (LA 60 mg) and long-acting propranolol 80 mg (LA 80 mg). Pharmacodynamic effects were evaluated in 34 healthy subjects by assessing heart rate, systolic blood pressure, and the product of heart rate and systolic blood pressure (double product) after exercise-induced tachycardia following both acute (day 1) and steady state (day 4) drug administration. The Cmax following administration of LA 60 mg was 9.5 and 11.4 ng/mL on days 1 and 4, respectively, compared with 18.8 and 20.0 ng/mL with 20 mg tid (P less than .0001). The tmax for LA 60 mg was significantly later (P less than .0001) than for conventional propranolol. Additionally, the apparent plasma half-life was significantly longer (P less than .0001) than with conventional propranolol. The LA 60-mg formulation was dose proportional to the LA 80-mg formulation. Pharmacodynamic evaluations showed no significant differences between LA 60 mg and 20 mg tid at any times tested with either acute or steady state dosing. This study demonstrates that LA 60 mg displays characteristics of a sustained-release formulation, is proportional with LA 80 mg, and produces pharmacodynamic effects that are similar to 20-mg tid dosing.

Administration, Oral↗
PubMed1987

Effects of the non-steroidal anti-inflammatory drugs, piroxicam or sulindac, on the antihypertensive actions of propranolol and verapamil.

Twenty-five hypertensive patients participated in a randomized placebo-controlled study. After blood pressures were normalized with propranolol or verapamil alone over a 6-week period, patients were entered into a 4-week double-blind period where they received non-steroidal anti-inflammatory drug (NSAID) treatment (sulindac or piroxicam) or placebo treatment in addition to their antihypertensive therapy. There was a significant elevation in standing systolic blood pressure (P less than 0.05) with propranolol and sulindac, when compared with propranolol and placebo, but no significant changes were shown with propranolol and piroxicam. Systolic blood pressures on sulindac treatment were significantly lower (P less than 0.05) in both supine and standing positions during treatment of hypertension with verapamil compared with propranolol. Both supine systolic and diastolic blood pressures on piroxicam treatment were significantly lower (P less than 0.05) during treatment of hypertension with verapamil compared with propranolol. We conclude that NSAID transiently block the antihypertensive effect of propranolol, causing blood pressures to increase and side effects to improve. However, NSAID do not cause loss of antihypertensive control with verapamil.

Adult↗
PubMed1986

Pharmacokinetics of ranitidine in patients with renal failure.

The pharmacokinetics of ranitidine were studied in ten patients with renal failure (creatinine clearance, 6-54 mL/min) after intravenous (IV) (50 mg) and oral doses (150 mg). After oral administration, peak plasma concentrations of 378-808 ng/mL were obtained in two to six hours. Plasma concentrations declined very slowly and concentrations greater than 100 ng/mL were obtained for 16 to 20 hours after the dose. The elimination half-life following oral administration was 8.5 +/- 2.8 hours (standard deviation [SD]), and the bioavailability of ranitidine was 43.3% +/- 10.5%. After IV administration, the elimination half-life, plasma clearance, renal clearance, and volume of distribution were 7.0 +/- 1.0 hours, 170 +/- 38 mL/min, 36.0 +/- 25.0 mL/min, and 1.3 +/- 0.4 L/kg, respectively. About 20% of the IV dose and 9% of the oral dose were recovered unchanged in urine. There was a significant correlation between the renal clearance of ranitidine and creatinine clearance (r = .74, P less than .05) after IV administration. The elimination half-life in patients with renal insufficiency is about three times greater than that reported in the literature for healthy subjects. Similarly, the plasma clearance in these patients is about 20% of that reported in healthy subjects. The results indicate that ranitidine elimination is appreciably reduced in renal failure and that an adjustment of dose in patients with renal failure is warranted. A dose of 75 mg bid may be adequate in maintaining the therapeutic plasma concentrations that are required for adequate H2-blocking activity.

Aged↗
PubMed1986

Gastrointestinal blood loss in arthritic patients receiving chronic dosing with etodolac and piroxicam.

Etodolac, a new anti-inflammatory analgesic drug found to be effective in treating arthritis in a dose range of 100 to 300 mg bid, has been shown to induce significantly less gastrointestinal microbleeding in normal men than several other NSAIDs. In this study, the effect on gastrointestinal blood loss of high-dose etodolac, 300 and 500 mg bid, versus piroxicam at its normal therapeutic dose of 20 mg qd, was investigated by the 51Cr method in 23 men with osteo- or rheumatoid arthritis. Placebo periods preceded and followed 28 days of active drug treatment. Blood and stool analyses were performed by an analyst not aware of drug assignment or study design. Patients receiving piroxicam, but not those receiving either dose of etodolac, had a significantly higher mean level of fecal blood loss in the active treatment phase compared with the pretreatment placebo level (p less than 0.01). Further, microbleeding was significantly greater for the piroxicam group during treatment than for either of the etodolac groups (p less than 0.01). There were no significant differences in fecal blood loss between the two groups receiving etodolac compared with pretreatment. Even at doses two to three times those found effective in the treatment of arthritis, etodolac produces no increase in fecal blood loss, in contrast to blood loss seen with the recommended dose of piroxicam. Fecal blood loss in osteoarthritic patients, not receiving an NSAID, was similar to normal subjects in previous studies.

Acetates↗
PubMed1986

Antihypertensive effect of doxazosin in hypertensive patients: comparison with atenolol.

The antihypertensive effect of doxazosin 1-16 mg once-daily was compared with that of atenolol 50-100 mg once-daily, and placebo, utilizing a double-blind parallel group (12 patients each) design. Blood pressure (BP) and pulse rate were determined in out-patients who returned for clinic visits every 2 weeks for 14 weeks. During the first 4 weeks, all patients received single-blind placebo therapy. During the subsequent 10 weeks, patients were randomized to placebo, atenolol or doxazosin treatment. After 2 weeks of doxazosin therapy 16 mg daily, there was a significant decrease from baseline (single-blind placebo period) in supine diastolic BP (P less than 0.01) and standing diastolic BP (P less than 0.001). The decreases in supine and standing diastolic BPs in the doxazosin 16 mg daily group were significantly (P less than 0.01) different from the corresponding BPs of the placebo group. At weeks 12 and 14, heart rates in the doxazosin group were not significantly different from baseline or from those in the placebo group. After 4 and 6 weeks of atenolol 100 mg daily, there was a significant decrease from baseline in both supine (P less than 0.001 and P less than 0.05) and standing (P less than 0.05) diastolic BPs and heart rates (P less than 0.05). However, when the atenolol group was compared with the placebo group, a significant decrease occurred only with supine diastolic BP at week 12 (P less than 0.01) and not at week 14; but significant decreases occurred in supine and standing heart rates at weeks 12 and 14 (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗