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Biomedical subjects

G Levy

Publications and source records attributed to G Levy.

At least 397 records · Page 22Linked to original sources
PubMed1979

Comparative pharmacokinetics of coumarin anticoagulants. XLII: Effect of phenobarbital on systemic availability of orally administered dicumarol in rats with ligated bile ducts.

The purpose of this investigation was to determine if the previously demonstrated inhibitory effect of phenobarbital treatment on the systemic availability of orally administered dicumarol in rats is related to the known effect of phenobarbital on bile output. It was found that phenobarbital had no apparent effect on the systemic availability of an aqueous dicumarol suspension in rats with ligated bile ducts. Compared to results obtained previously on normal rats, bile duct-ligated rats absorbed and eliminated dicumarol much more slowly and absorbed much less of the anticoagulant. On the other hand, the relative inductive effect of phenobarbital treatment on dicumarol elimination was similar in normal and in bile duct-ligated animals. The latter exhibited substantial serum transaminase elevations, indicative of liver damage presumably secondary to cholestasis. These results demonstrate that a drug-drug interaction can depend markedly on the pathophysiological status of the animals.

Animals↗
PubMed1979

Effect of heparin injection on plasma protein binding of bilirubin and salicylate in rats.

Intravenous heparin injection significantly increased the free bilirubin and salicylate fractions in the plasma of rats. This effect occurred within 2 min after injection of 500 U of heparin/kg and lasted for 15--45 min (bilirubin) or for greater than 45 min (salicylate). In vitro addition of heparin to plasma had no quantitatively significant effect on the protein binding of bilirubin and salicylate. The in vivo effect of heparin on protein binding was reversible by treating the plasma with activated charcoal, a procedure known to remove fatty acids from albumin. Since protein binding affects the pharmacokinetic characteristics and the pharmacological activity of drugs, the heparin--drug interaction may have significant clinical implications. Use of heparinized plasma for exchange transfusion in the treatment of neonatal jaundice may be hazardous.

Anesthesia↗
PubMed1979

Comparative pharmacokinetics of coumarin anticoagulants XLIII: Concentration-dependent hepatic uptake of warfarin in rats.

The purpose of this study was to determine if hepatic warfarin uptake, which has a major quantitative effect on warfarin distribution in rats, is concentration dependent. Adult male rats received either 0.1 or 1.0 mg of racemic warfarin/kg iv and were killed 6 hr later. With increasing dose, the concentrations of free and total (free plus protein-bound) serum warfarin increased much more than proportionally, and the total warfarin concentration in the liver increased much less than proportionally. The liver to serum total warfarin concentration ratios 6 hr after injection of the 0.1- and 1.0-mg/kg doses were 11.3 +/- 1.7 and 0.814 +/- 0.222, respectively (mean +/- SD, n = 6, p less than 0.001). The ratio of the total drug concentration in the liver to the free drug concentration in serum (mean +/- SD) was 866 +/- 105 in animals that received the 0.1-mg/kg dose and 111 +/- 42 in animals that received the 1.0-mg/kg dose (p less than 0.001). It is concluded that hepatic warfarin uptake decreases with increasing drug concentration and that this may cause the apparent volume of distribution of warfarin to decrease with increasing dose in rats.

Animals↗
PubMed1979

Accumulation kinetics of drugs with nonlinear plasma protein and tissue binding characteristics.

The purpose of this investigation was to study, by digital computer stimulation, the accumulation kinetics of drugs which exhibit concentration-dependent binding to tissues and either linear (constant free fraction) or concentration-dependent (increasing free action with increasing drug concentration) binding to plasma proteins. It was assumed that elimination rate is proportional to free drug concentration in plasma and that there occurs instantaneous equilibration of drug between vascular and nonvascular spaces. Nonlinear binding can yield, under certain conditions, apparently biexponential plasma concentration-time curves which may be misinterpreted as being representative of a linear and biexponential system. Such misinterpretation would cause the following errors in the prediction of drug accumulation and elimination kinetics during and after constant-rate infusion: (a) the time required to reach steady state may be overestimated, and (b) the prominence of the apparent distribution phase after cessation of infusion may be underestimated. Drugs with linear and nonlinear plasma protein binding characteristics differ with respect to the relaionship between infusion rate and steady-state concentration. This relationship is linear when plasma protein binding is linear. Steady-state concentration increases less than proportionally with increasing infusion rate if plasma protein binding is drug concentration dependent.

Blood Proteins↗
PubMed1979

Determination of naproxen and its desmethyl metabolite in human plasma or serum by high performance liquid chromatography.

1. A liquid chromatographic method has been developed for the simultaneous determination of the anti-inflammatory agent naproxen and its metabolite, 6-0-desmethyl-naproxen, in human plasma or serum. 2. After addition of p-chlorowarfarin as the internal stardard, plasma is acidified and extracted with either chloroform (for assay of naproxen only) or ethyl acetate (for assay of naproxen and desmethyl-naproxen), the organic solvent is evaporated, the residue is dissolved in acetonitrile and injected onto a reverse phase column coupled with an ultra-violet absorbance detector. 3. Drug and metabolite can be detected readily in concentrations above 2 micrograms per ml in 0.5 ml samples. Salicylic acid and its metabolites and a number of other durgs were found not to interfere with the assay.

Chromatography, High Pressure Liquid↗
PubMed1979

Pharmacokinetics of heparin. II. Studies of time dependence in rats.

The purpose of this investigation was to determine whether the time course of heparin activity (bioassayed heparin concentration) in plasma of rats during and after constant rate i.v. infusion of heparin can be predicted from the pharmacokinetic characteristics of a single i.v. bolus dose of heparin administered to the same animals. Five rats received a rapid i.v. injection of heparin, 320 to 517 U/kg, and on the following day, an i.v. infusion of heparin, 2.7 to 4.0 U/min/kg, for 10 to 11 hr. Heparin activity in plasma at the end of the infusion was about twice as high as predicted on the basis of the total clearance of the bolus dose. Even though the maximum heparin activity immediately after the bolus dose and at the end of the infusion were similar, the biologic half-life of heparin at the end of the infusion was about twice as long as that of the bolus dose. Apparently, the pharmacokinetics of heparin are time dependent. This may explain, at least in part, the clinical observation that heparin infusion rate must often be reduced after the initial days of therapy.

Animals↗
PubMed1979

[Hemodilution in vitro and parameters of hemostasis].

High molecular weight (approximately 60,000) dextran having been selected in a protocol of per-operative hemodilution, a prior study was undertaken in vitro in order to measure the variations in parameters of hemostasis. Factor of primary hemostasis, of plasma coagulation and fibrinolysis were thus evaluated in control blood samples, not diluted and diluted to 1/5 th by dextran or by a buffer solution. Statistical analysis was carried out using the t-test for pairs of variables. The following emerge from the results: 1 - an absence of difference with regard to the fibrinolytic activity of the plasma, but marked fragility of the fibrin clot in the presence of dextran; 2 - variations for plasma coagulation factors due to dilution; 3 - acceleration of the phase of polymerisation of fibrin monomeres and a decrease in platelet stickiness and aggregation due to dextran.

Blood Coagulation↗