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Biomedical subjects

C Revillard

Publications and source records attributed to C Revillard.

9 recordsLinked to original sources
PubMed1978

[Role of metabolites in the relationship between pharmacokinetics and the effect of beta blockers. Studies on tolamolol and bufuralol].

Plasma concentrations of tolamolol and bufuralol (beta-blocking agents) were measured after oral and intravenous administration to healthy volunteers. The plasma levels of their main metabolite was also determined. Simultaneously, the effect of the drugs on the heart rate and blood pressure was monitored under various stimuli (isoproterenol, exercise or orthostatism) and Valsalva maneuver. When given orally, the two drugs are extensively metabolized by a hepatic first-pass effect. After reaching the systemic circulation, they are metabolized in the liver to hydroxylated derivatives with similar pharmacologic activity as the parent molecule. For tolamolol it is possible to demonstrate a good correlation between parent drug blood levels and the pharmacodynamic effect; this relation is less evident for bufuralol. The pharmacokinetic analysis of the behaviour of the two beta-blocking agents and their main metabolite makes it possible to explain this difference in part. The results of the present study emphasize the importance of measuring metabolites when dose-action relationships are investigated.

Administration, Oral↗
PubMed1977

[Side effects of nalidixic acid in a patient with severe renal failure. Clinical study and proposal of a pharmacokinetic model].

Side effects due to ingestion of nalidixic acid in a 46 year old patient with phenacetine-induced interstitial nephritis and severe renal failure are reported. This observation underlines the point that, besides the direct neurotoxic effect of nalidixic acid, disturbance of the acid-basic equilibrium could be seen in patients with renal failure in particular. A hypothetical pharmacokinetic model suggests that two metabolites of nalidixic acid could provide enough hydrogen ion to induce acidosis in cases of renal failure.

Acid-Base Imbalance↗
PubMed1976

[Pharmacokinetics of two beta blocking drugs: detection of a pharmacogenetic abnormality].

10 healthy male volunteers received orally either 100 mg tolamolol or 20 mg bufuralol. These experiments were repeated by intravenous administration of 10 and 5 mg respectively of these two drugs. Plasma levels of the parent drugs and their main metabolite were measured. In one subject, the apparent half-life of elimination was increased from 2.5 h (normal subjects) to 5 h for both drugs. This prolongation of the half-life is associated with low plasma levels of the metabolites, a peculiarity which can be explanined by a decreased rate of metabolism for these two drugs. This anomaly may explain the marked orthostatic hypotension observed only in this subject. The likelihood of a pharmacogenetic defect is discussed.

Administration, Oral↗
PubMed1976

[Clinical pharmacokinetics].

The action of a drug depends on the quantity which reaches the site of its pharmacological action and how long it remains there. The necessary vital processes of the body dilute the active principle into different compartments of distribution, transform it into metabolites, and excrete it. Since a time duration of drug presence at the site of action is vital for the cure of disease, a comprehensive and quantitative expression of these time courses of drug distribution as a function of dose and route of administration is necessary for the establishment of proper dosage regimens for the treatment of disease and the avoidance of toxicities. The purpose of pharmacokinetics is to study these phenomena and to construct models suitable to explain them and to predict the behavior of drugs in conditions not yet studied. In this review some basic principles of pharmacokinetics (i.e. the compartment, the volume of distribution, the elimination half-life, etc.) are explained. Their clinical implications are shown in the case of multiple dose administration and in the study of the relations existing between blood levels of digoxin and the pharmacological action of this drug.

Body Weight↗
PubMed1975

A strategy of approaching the fit of a compartmental model applied to the behaviour of aspirins in humans.

A compartmental model has been set up with five parts. Formulation and testing of the model have been performed by simultaneous experiments involving measurement of blood levels of ASA and SA for four different preparations of aspirin investigated in four different patients. The hypotheses of the present study had been based upon a four-compartment model. However, such a model did not appear to be adequate and a new model with five compartments has been substituted for the former one. The five-compartment model has led to the formulation and testing of new physiological hypotheses; it has also provided the development of a fitting method using powerful convergence algorithms. A general analytical formulation has been set up which has made it possible to circumscribe the multiple roots of the characteristic polynomial when they have to be taken into consideration.

Aspirin↗