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Biomedical subjects

D J Sumner

Publications and source records attributed to D J Sumner.

At least 55 records · Page 3Linked to original sources

Comparative pharmacokinetics and pharmacodynamics of cardiac glycosides.

1 The pharmacokinetics and pharmacodynamics of ouabain, digoxinn and beta-methyl digoxin (medigoxin) have been investigated in a crossover study in four normal healthy volunteers. 2 Pharmacokinetics were studied using [3H]-labelled glycosides and the shortening of the left ventricular ejection time (LVET) was used as a measure of the effect of the drugs. A graded exercise protocol was used to correct for the effects of heart rate on LVET. 3 In three of the four subjects, both digoxin and beta-methyl digoxin produced a shortening in the LVET, but no such change could be detected with ouabain in any of the four subjects. 4 There was a good linear correlation between the shortening of the LVET and the amounts of digoxin or beta-methyl digoxin present in the body tissues. 5 One subject who showed no drug-related LVET shortening had greatly enhanced clearances of all three drugs studied.

Adult↗

A pharmacokinetic and clinical evaluation of iron poly (sorbitol-gluconic acid) complex.

The pharmacokinetics of iron poly (sorbitol-gluconic acid) complex (IPSG) were studied following a single intramuscular injection of 59Fe-labelled IPSG to 4 iron deficient-patients. The results showed a more rapid uptake of iron from the site of injection than that reported with iron dextran while there was a lower urinary excretion than found with iron sorbitol citrate. A clinical study was carried out in 11 patients with iron deficiency anaemia. Patients were allocated at random to receive IPSG as either 250 mg or 500 mg elemental iron per week for 8 weeks. A satisfactory response to therapy was obtained with each regimen whether measured by an increase in haemoglobin concentration or in serum ferritin concentration. Few side-effects were encountered but discomfort and staining at the injection site was found on the higher dose schedule.

Anemia, Hypochromic↗

Computer-assisted review of digoxin therapy in the elderly.

Current practice with digoxin was assessed in a group of 42 elderly patients by comparing plasma digoxin concentrations attained on previously established maintenance doses with those generated by a computer programme designed to calculate dosage schedules to suit individual patients. Discrepancies between measured and computed plasma levels and between established and computed doses dictated withdrawal of the drug or revision of dosage in 26 patients (62%), with obvious clinical benefit. An important determinant of dosage was renal function; reduction in creatinine clearance provided good evidence for the loss of ability of the elderly kidney to eliminate digoxin. Simple bedside methods are available which permit a reliable estimate of creatinine clearance without a 24-hour urine collection, provoding a rational basis for the choice of digoxin dosage in the elderly.

Aged↗

Digoxin pharmacokinetics: multicompartmental analysis and its clinical implications.

The kinetics of digoxin have been investigated in healthy volunteers using an isotopic tracer technique. A three compartment open kinetic model has been proposed as the simplest model consistent with the plasma, urinary and faecal data obtained. The renal clearance of digoxin (mean +/- s.d.) was found to be 119+/-10 ml/min, which did not differ significantly from the glomerular filtration rate (110+/-14 ml/min). Digoxin extra-renal clearance (mean+/-s.d.) was found to be 47+/-7 ml/min. The model predicts that the tissue concentration attained after four 0.25 mg oral doses spread over 24 h can be achieved within a period of 4 h following a single oral loading dose of 1 mg. Maintenance doses can be derived from a simple formula based on the glomerular filtration rate, extra-renal clearance and bioavailability of the digoxin preparation used.

Adult↗

Tests of pancreatic function using 75Se-selenomethionine.

Pancreatic function was investigated in 43 patients using a combination of conventional and subtraction scans of the pancreas and duodenal aspiration of the 75Se-Selenomethionine injected, in the time periods 60-150 minutes, 90-120 minutes and 105-150 minutes after injection. Patients with chronic alcoholism, chronic pancreatitis, pancreatic carcinoma, extrahepatic biliary obstruction and liver disease were included. Seven patients with no evidence of gastro-intestinal disease served as controls. Pancreatic scanning provided eight false positive and two false negative results (23.3%) and with 75Se-Selenomethionine excretion at 105-150 minutes, six false results were obtained (14%). In only one patient was a false positive result obtained with both scans and the 75Se-Selenomethionine test. The performance of conventional and subtraction scans of the pancreas with measurement of 75Se-Selenomethionine activity in the duodenal aspirate collected from 105-150 minutes after injection provides a convenient means of testing pancreatic exocrine function in a single three hour session.

Alcoholism↗

Determination of platelet and fibrinogen half-life with [75Se]selenomethionine: studies in normal and in diabetic subjects.

1. Simultaneous platelet and fibrinogen survival studies were carried out on a group of seven normal persons and eleven diabetic patients. 2. Survival time was calculated: (a) by measuring the interval between 50% of the maximum radioactivity in the anabolic phase and 50% of the maximum radioactivity in the catabolic phase, and (b) by fitting an exponential function to the decay phase of the curve. 3. With the first method, the normal group had a mean plaetelet survival which did not differ significantly from that in the diabetic group. With the second method, however, the platelet half-life in the diabetic patients was significantly shorter than in the normal subjects. 4. Fibrinogen survival was significantly shorter in the diabetic group with either method. 5. It is concluded that there is an increased utilization of platelets and fibrinogen in diabetic subjects.

Adult↗

Measurement of diastolic closure rate of normal mitral valve.

Published values for the diastolic closure rate of the normalmitral vary and reflect diffference in methods of recording and measurement. From strip chart records it was concluded that the form of the recorded mitral diastolic closure slope can vary, that reproducible measurements of the closure rate can be made from echograms in which diastolic closure approximates closely to a monophasic form, that the amplitude of these echograms is maximal, and that their closure movements remain essentially monophasic at chart speeds up to 100 mm/s. Measuring only complexes with essentially monophasic closure movements, the within and between-subjected variation of the normal mitral diastolic closure rate was investigated. The ranges obtained from multiple measurements in a single subject and from a group of 45 normal subjects were comparable but the distribution of the results differed. It was concluded that there was a real between-subject variation in the normal mitral diastolic closure rate and that the diastolic closure rate in a single subject should be determined by measurement of a series of complexes. The accuracy of measurement of the diastolic closure rate of the normal mitral valve has been improved by using strip chart records and by measuring only echograms in which diastolic closure approximates closely to a monophasic form.

Adolescent↗

The renal clearance of disopyramide after bolus intravenous injection.

Following bolus intravenous injection of disopyramide in eight normal volunteers the renal clearance of the drug appeared to fall with time. In the first two hours after injection renal clearance had a mean value of 89.0 ml min-1 and fell to 29.4 ml min-1 between 48 and 72 h. In a separate study disopyramide was given by continuous intravenous (i.v.) infusion for 8 h following a loading dose of the drug. Renal clearance of disopyramide was thus estimated hourly over three narrow serum concentration ranges in a single volunteer. The estimate of renal clearance of the drug over the first hour following the start of these infusions was considerably in excess of values obtained later in the experiments. The change in disopyramide renal clearance following bolus injection is partially time-dependent. There are, however, fallacies in calculating short-term clearance values after bolus drug injection from the venous concentration-time curve and these may partially explain the change in renal clearance of disopyramide with time.

Disopyramide↗