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Biomedical subjects

L Dodion

Publications and source records attributed to L Dodion.

8 recordsLinked to original sources
PubMed1988

Acute and chronic effects of torasemide in healthy volunteers.

The acute and chronic effects of torasemide (1-isopropyl-3- ([4-(3-methyl-phenylamino)pyridine]-3-sulfonyl)urea) were investigated in 2 separate groups of healthy volunteers: 1. In a first group of 6 volunteers, the acute effects of torasemide were investigated at 3 different steady state plasma and urinary drug levels and compared to those of furosemide according to a randomized cross-over design. Each drug was continuously given by i.v. route in 3 consecutive periods of 90 min immediately after a control run-in period of 90 min. The last 30 min period of each control and 3 drug administration periods fulfilled the steady state conditions and were used for clearance determinations and plasma and urinary concentrations of drug. The plasma levels of both torasemide and furosemide increased progressively at increasing plateaus during each of the 3 drug periods with no significant difference between each of the 2 drugs. However, the urinary drug excretions were 5 times lower with torasemide than with furosemide. In spite of these highly different urinary drug concentrations, torasemide and furosemide induced a similar increase of the water excretion, osmolar and creatinine clearances and absolute and fractional excretions of sodium, potassium, chloride, calcium and magnesium. The correlation between the logarithm of the drug doses and the urinary effects were highly significant with both drugs. Free water clearance was stable throughout the torasemide administration, whereas it increased steadily with each dose of furosemide. The fractional distal chloride reabsorption decreased significantly more with torasemide than with furosemide.(ABSTRACT TRUNCATED AT 250 WORDS)

Chromatography, High Pressure Liquid↗
PubMed1986

Diuretic activity, safety and pharmacokinetics of torasemide during chronic treatment in normal subjects.

Torasemide 40 mg/day p.o. was administered for 21 days to 8 healthy volunteers to investigate its pharmacodynamics, pharmacokinetics and safety on chronic administration. It induced a highly significant initial increase in 24-h urinary volume and 24-h excretion of sodium and chloride, but its affect diminished after the first days. On Days 0, 1, 10 and 21 the experiment was divided in 3 clearance phases, extending from 0 to 2 h, 2 to 6 h and 6 to 24 h after dosing. The fractional excretion of sodium, chloride, potassium, calcium, magnesium and inorganic phosphates peaked during the first 2 h and returned almost to the control value during the following two clearance phases. The phase-dependent changes were significant for all electrolytes, except for potassium and inorganic phosphate. Plasma electrolyte levels remained constant throughout the study, except for a small decrease in chloride and potassium and for an increase in calcium and magnesium. Fasting blood glucose and glucose tolerance test were unaffected. A small but significant decrease in LDL-cholesterol was observed on Day 10. Other plasma lipid components showed minor changes. Plasma uric acid levels were moderately increased. There was no significant change of the creatinine clearance. Body weight fell significantly (by about 2 kg) during the study. Tonal audiometry was normal before and after the study. There was no significant difference between the plasma levels of torasemide on Days 1, 10 and 21, nor between its elimination half-life on Days 1 and 21. Side-effects consisted mainly of fatigue and low-back pain on days of intense diuresis.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1986

A comparison of the pharmacokinetics and diuretic effects of two loop diuretics, torasemide and furosemide, in normal volunteers.

The diuretic effects of torasemide and furosemide at three different steady-state plasma and urinary drug levels were compared in a randomized cross-over study in 6 healthy volunteers. Each trial with either torasemide or furosemide consisted of four consecutive periods of 90 min, the first being a control period, and during the three other periods, increasing doses of drug were administered. Each 90-min period was itself divided into three 30 min blood sampling and urinary collection periods. The urinary losses of water and electrolytes were compensated within each 30-min period by intravenous infusion of saline (NaCl) and 5% glucose solutions, to which KCl was added. A constant dose of calcium gluconate was given to compensate, at least in part, any calcium loss. Data from each 30 min control and the 3 drug dose periods, corresponding to full steady-state conditions, were used for clearance determinations and measurement of plasma and urinary drug concentrations. Urine volume, osmolar clearance, absolute and fractional urinary excretion of sodium, potassium, chloride, calcium and magnesium and creatinine clearance increased similarly after torasemide and furosemide according to the logarithm of the dose of the drug. Free water clearance stabilized at a constant level with torasemide and increased continuously after each dose of furosemide. During each of the three drug administration periods, the plasma levels of torasemide were not significantly different from those of furosemide, whereas the urinary concentrations and absolute excretion rates of torasemide were more than 5-times lower than those of furosemide.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1979

Bioavailability study of gitoxin in a solid dosage form.

Although the cardiotonic activity of gitoxin is known for almost half a century, this digitalis glycoside has never been used in therapy, due to its apparent lack of resorption after administration by oral route. Recent studies have demonstrated that the bioavailability of gitoxin could be upraised to 100% provided it be given as a hydroalcoholic solution. The present paper deals with the development of a solid dosage form (tablets) using a physical association of gitoxin and sodium escinate.

Adult↗
PubMed1978

Metabolic and pharmacokinetic studies on Bamifylline. A review.

The metabolic fate and pharmacokinetics of Bamifylline have been investigated by high performance liquid- and gas-chromatography techniques and radio-isotopic methods in several experiments following oral and intravenous administration of single and repeated doses of 300 mg, 600 mg and 900 mg of this drug. The 300 mg single- and multiple-dose experiments were performed by comparing Bamifylline with 200 mg of Theophylline within the confines of controlled double-blind randomized cross-over studies. Bamifylline is catabolized into several closely related compounds and into sulpho- and glucurono-conjugates of an hydroxylated derivative. Its metabolites are rapidly and extensively excreted via the kidneys and the liver. Only the unchanged Bamifylline has been recorded in the blood following administration of the radio-labelled parent compound. Bamifylline achieves peak plasma levels more rapidly than Theophylline. The half-time of Bamifylline plasma concentrations ranges from 1.5 hours to 2.0 hours, which is appreciably shorter than that of Theophylline which exceeds four hours. By further contrast the distribution volumes of Bamifylline are three to ten times larger than those of Theophylline. No evidence of cumulation has been found in blood following the repeated administration off doses as high as 900 mg administered at intervals of eight hours.

Adult↗
PubMed1977

[Experimental models for the pharmacologic study of anti-arrhythmia drugs].

In order to assess the value and therapeutic safety of an antiarrhythmic drug, it must be submitted to multiple tests, which reproduce as faithfully as possible the conditions observed in human pathology. The main experimental approaches are presented here: screening and control tests. For each test, the authors emphasize the various experimental factors limiting their interpretation and allowing the extrapolation to men.

Aconitine↗