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P Pellegrin

Publications and source records attributed to P Pellegrin.

16 recordsLinked to original sources
PubMed1986

Site of action of torasemide in man.

The effect of torasemide, a new orally and parenterally active diuretic agent, on the renal mechanisms of dilution and concentration was studied in 6 healthy volunteers. The experimental conditions included water and osmotic diuresis. Torasemide caused maximal chloruresis and natriuresis during the 20-40 min after administration. The effect was more pronounced under osmotic diuresis and persisted throughout the 100 min of those experiments. A distinct effect both on free water clearance (CLH2O) during water diuresis and tubular reabsorption of solute free water (TcH2O) during osmotic diuresis strongly suggests that the major site of action of torasemide is the ascending limb of the loop of Henle. Comparison with furosemide under osmotic diuresis indicates longer abolition of TcH2O/GFR by torasemide in keeping with the fact that its half-life is 2- to 3-times longer than that of furosemide.

Adult↗
PubMed1983

Hepatic clearance of gitoxin: pharmacokinetic study on rabbit isolated liver. Influence of protein binding and comparison with digoxin.

Hepatic clearance of gitoxin has been studied in the rabbit and compared with that of digoxin using an isolated perfused liver technique. During 1.5 hour perfusions with a modified Krebs-Henseleit solution, gitoxin perfusate levels decreased biexponentially; the distribution and elimination half-lives were estimated to be 0.14 and 1.25 hour, Vd area to be 95.5 ml.g-1 and intrinsic metabolic clearance to be 1.98 ml.min-1.g-1. During 1.5 hour perfusions with modified Krebs-Henseleit solution containing 2.7% bovine serum albumin, gitoxin perfusate levels decreased monoexponentially. This is probably due to protein binding which moderates hepatic uptake so that distribution is not yet complete after 1.5 hour and it is therefore impossible to discriminate the two phases. This was confirmed by 5 hour perfusion experiments with an emulsion of perfluorocarbon in the modified Krebs-Henseleit solution also containing 2.7% bovine serum albumin, during which gitoxin levels decreased biexponentially. Distribution and elimination half-lives have been estimated to be 0.31 and 5.54 hours, Vd area to be 139 ml.g-1 and intrinsic metabolic clearance to be 1.36 ml.min-1.g-1. Gitoxin has been compared in these experimental conditions with digoxin, one of the most often used cardiotonic's. Distribution and elimination half-lives of digoxin were estimated to be 0.34 and 4.52 hours, Vd area to be 46.5 ml.g-1 and intrinsic metabolic clearance to be 0.17 ml.min-1.g-1. Other pharmacokinetic parameters (alpha, beta, V1, V2...) also have been calculated for these three types of perfusion experiments.

Animals↗
PubMed1979

The binding of gitoxin to human plasma proteins.

The binding of gitoxin, digitoxin and digoxin to human plasma proteins was measured by ultracentrifugation and equilibrium dialysis. At concentrations in the range of therapeutic plasma levels, protein binding amounted, respectively, to 85, 92 and 20%, the last two values being consistent with data reported in the literature. The affinity of purified human albumin was not significantly different for the three cardiac glycosides tested. No other protein than albumin was found to bind gitoxin in human plasma.

Blood Proteins↗
PubMedDate not supplied

[Hepatic clearance of drugs. Physiological and pharmacokinetic considerations].

The aim of the first part of this work is to present elements of hepatic cytology and physiology in order to demonstrate the organisation of the liver for the metabolisation of drugs: the cytology of hepatocytes, their arrangement in the parenchyma, the hepatic microvascularisation, the distribution of the metabolic reactions in the hepatic acinus and the structure of the biliary tract involved in the elimination of some metabolites. 2. The second part is devoted to the concept of hepatic clearance. A few considerations are presented about physiological aspects (hepatic uptake), followed by a more extensive chapter about pharmacokinetics. The following points are explained: mathematical terms of clearance, physiological models, hepatic first-pass effect, influence of the hepatic clearance on half-life of a drug and area under the curve of concentration versus time, the use of clearance or half-life as index of hepatic metabolism and a classification of the drugs in correlation with their hepatic clearance. 3. The conclusions present some contradictions and unresolved points persisting, at the present time, in the hepatic clearance theories and propose new approaches for future investigations.

Animals↗