The heart rate response to atropine in uremic patients, obese subjects before and during fasting, and patients with other chronic illnesses.
Explore the source record for details and available documents.
Acetylcholine↗
Biomedical subjects
D T Lowenthal
Publications and source records attributed to D T Lowenthal.
Therapeutic studies in NZB/W mice. III. Relationship between renal status and efficacy of immunosuppressive drug therapy.
Female NZB/W mice develop a disease closely resembling human systemic lupus and serve as an animal model for therapeutic studies. Several previous studies have demonstrated the efficacy of different immunosuppressive drug regimens in the therapy of glomerulonephritis in NZB/W mice. After the onset of immune complex deposition, treatment with intermittent high doses of cyclophosphamide or daily low doses of the combination of cyclophosphamide, azathioprine, and methylprednisolone has been effective. The present study was designed to compare such effective regimens in mice early in the course of their renal disease versus mice late in the course of glomerulonephritis. One to three injections of high-dose cyclophosphamide during active immune complex deposition and early histologic changes were significantly effective in prolonging survival, whereas treatment late in the course of glomerulonephritis was less effective. Even more striking was the result of low-dose combination therapy. Daily treatment with cyclophosphamide, azathiprine, and methylprednisolone (C + A + M) effectively prolonged survival when started in mice 5 months old, but was of no benefit when started in those 8 months of age. In a concluding experiment, older mice were selected on the basis of degree of renal disease and studied with regard to proteinuria and survival. Those with mild renal disease responded to daily treatment for 6 months with C + A + M at 1 mg/kg of each drug, whereas those with advanced renal disease at the onset of therapy did not benefit.
Age Factors↗
The diuretic response in normal volunteers to a new benzylamine, 2-aminomethyl-4-(1,1-dimethylethyl)-6-iodophenol HCl.
A phase I dose-response study of 2-aminomethyl-4-(1,1-dimethylethyl)-6-iodophenol HCl (MK-447) was performed with the following oral doses: 6.25, 12.5, 25, 50, and 100 mg. Each volunteer served as his own control. The study was carried out in double-blind fashion on a 5-Gm Na and K diet with a minimum 2000 ml fluid intake. Urine was fractionated and analyzed for sodium, chloride, potassium, calcium, uric acid, and volume. Comparisons (MK-447 minus control values) of the 24-hour total sodium, calcium, potassium, and volume excretion rates at 6.25, 25 and 100 mg MK-447 were as follows: sodium, 195, 345, and 528 muEq/min; chloride, 191, 365, and 756 muEq/min; potassium, 77, -3, and 65 muEq/min; and volumes, 1, 3.4 and 11.7 ml/min. MK-447 did not alter calcium excretion. Uric acid excretion was observed to decrease as the dose of MK-447 was increased, however, the serum uric acid level always remained within normal limits. MK-447 did not alter the physiologic parameters but did produce symptoms of volume contraction at 100 mg. Because no further dose increase was attempted, a plateau in the dose-response curve was not reached. Comparison of 100 mg MK-447 with 80 mg oral furosemide revealed similar potency and a somewhat longer duration of action for MK-447.
Butylated Hydroxytoluene↗
The influence of food on the absorption and metabolism of drugs: an update.
Food-drug interactions can lead to a loss of therapeutic efficacy or toxic effects of drug therapy. Generally, the effect of food on drugs results in a reduction in the drug's bioavailability; however, food can also alter drug clearance. The benefits of considering metabolism and pharmacokinetic information in the drug discovery process have been highlighted by Humphrey and Smith (79) and the process of rational drug design should include considerations of the chemistry, pharmacology and pharmacokinetics of the drug (80) and the impact of diet on these parameters.
Biological Availability↗
The effects of exercise training on the pharmacokinetics of digoxin.
BACKGROUND: Studies have shown that digoxin binds to the working muscles during an acute bout of exercise, with a concomitant decrease in serum digoxin concentration. This study investigated the effects of 16 weeks of endurance exercise training on the pharmacokinetics of digoxin in old and young adults. METHODS: Twelve subjects, aged 68.5 +/- 4.5 years, and six subjects, aged 30.3 +/- 3.8 years, completed the study. All subjects were healthy, sedentary, and taking no cardiovascular medications. After initial testing and maximum oxygen consumption (VO2max) measurements, subjects were hospitalized for 28 hours for renal function testing and digoxin clearance studies and then randomly assigned to an exercise (EG) or control (CG) group. The EG completed 16 weeks (three 1-hour bouts/week) of aerobic training at 75% to 85% of maximum capacity. The CG did not exercise. All tests were repeated at the end of the 16-week study period. RESULTS: In the older EG subjects, VO2max increased by 3.4 ml/kg/min, or approximately 16% (P = 0.0002). VO2max increased in the younger EG subjects by 1.1 ml/kg/min, but the increase was not significant (P > 0.05). There were no significant changes in body composition, renal function, or time of onset, peak concentration, or elimination phase half-life of digoxin in either the old or young exercise or control groups (P > 0.05 for all variables). CONCLUSION: Although 16 weeks of endurance exercise training improves cardiorespiratory fitness, the pharmacokinetics of digoxin are neither improved nor adversely affected in healthy old and young adults.
Adult↗
Metabolism study of dihydro-alpha-ergocryptine,9,10-[9,10-3H(N)] in rat and human hepatocyte cultures and rat, monkey, and human microsomes.
An in vitro approach was undertaken to investigate the metabolite profile of dihydro-alpha-ergocryptine,9,10-[9,10 ( -3 ) H(N)] in humans by comparison with two species, rat and monkey, for toxicological studies. Hepatocytes (rat and human) and microsomes (rat, monkey, and human) were used in this study, and a high-performance liquid chromatography system was developed to determine the metabolic profiles. From the two in vitro metabolizing systems it was concluded that the compound was extensively metabolized in all species, with a similar overall rate of 4.5 ng/min/mg protein in the microsomal system. The human metabolite profile in hepatocytes showed an intersubject variability that was not confirmed with microsomes. The more complex human pattern consisted of eight metabolites (based on chromatographic properties) that were produced in rats (major part) or in monkeys. Of these eight metabolites, seven were produced by rat microsomes and six by the monkey microsomes. Because of qualitative and quantitative differences, it was not possible to show that the human metabolite profile was closer to the rat's or to the monkey's. The conclusion is that all the observed metabolites in human are produced either in rats (for a major part) or in monkeys, so that these two species cover the human metabolic pattern for toxicological studies.
Adult↗
The effects of delapril in combination with indapamide on glomerular filtration rate in elderly hypertensive patients.
We performed a placebo-controlled trial on the effects of a combined antihypertensive treatment with delapril, a new nonsulfhydryl angiotensin-converting enzyme inhibitor, and indapamide, a sulfonamide diuretic. We studied 28 elderly patients aged 65-85 years (mean age, 69 +/- 1 years) who took 30 mg delapril in combination with 1.25 mg indapamide once daily for 24 weeks. In the present study (performed simultaneously with our trial on the effects of delapril/indapamide on left ventricular mass in elderly patients with hypertension and on the same patients), we report the effects of this drug combination on glomerular filtration rate. Sitting arterial pressure (mean +/- SE) decreased from 156 +/- 1. 5/101 +/- 1 mm Hg at baseline to 133 +/- 1/73 +/- 1 mm Hg at the end of the 24-week treatment period (p < 0.0001). No significant changes in heart rate or episodes of orthostatic hypotension were observed. Glomerular filtration rate increased from 91.8 +/- 4.42 mL/min at baseline to 106.3 +/- 4.5 mL/min (p < 0.001) at the end of treatment. Our results show that the combination of delapril and indapamide is effective in the elderly hypertensive patient, with a favorable effect on the prevention of deterioration of kidney function.
Aged↗
Endoscopic evaluation of the effects of indobufen and aspirin in healthy volunteers.
This is an outcomes pharmacodynamic study using Nonsteroidal antiinflammatory agents, particularly acetylsalicylic acid (ASA), have been shown useful in various cardiovascular disorders, but they can be a major cause of iatrogenic gastrointestinal injury. Newer NSAIDs such as indobufen, an inhibitor of platelet aggregation that acts by reversibly inhibiting the platelet cyclooxygenase enzyme, have proven to be as effective as the older NSAIDs and appear to have a better gastrointestinal tolerability profile. When the gastroduodenal tolerability of 10 days of oral treatment with indobufen or ASA was assessed in healthy adult volunteers using endoscopic evaluation and the modified score scale of Lanza, only 1 of 18 (6%) volunteers who received indobufen had an increased erosion score at the completion of therapy, compared with 6 of 18 volunteers who received ASA (33%). Overall, both drugs were well tolerated. These results suggest that indobufen has a lower incidence of gastrointestinal effects than other NSAIDs and should be useful in the management of patients with cardiovascular disease.
Adolescent↗
Calculation of the rate of administration of parenteral medications as infusions.
Explore the source record for details and available documents.
Humans↗