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Biomedical subjects

G Levy

Publications and source records attributed to G Levy.

At least 415 records · Page 23Linked to original sources
PubMed1978

Pharmacokinetics of warfarin enantiomers: a search for intrasubject correlations.

The total body clearance of single doses of R(+)-, S(-)-, and racemic warfarin and the plasma concentration-anticoagulant effect curves for these drugs were determined in 10 healthy men, 21 to 51 yr old. This information was used to calculate the steady-state dose required to decrease prothrombin complex activity to about 30% of normal. This dose (mean +/- SD in mg/70 kg/day) is 17.8 +/- 9.3 for R(+)-warfarin, 6.63 +/- 2.19 for S(-)-warfarin, and 9.4 +/- 1.7 for racemic warfarin. There is a correlation between the maintenance doses of racemic and S(-)-warfarin (r = 0.89, p less than 0.01) but not between those of racemic and R(+)-warfarin (r = 0.30, NS). According to these calculations, the maintenance dose of racemic warfarin required by an individual patient may be a useful predictor of maintenance dose of S(-)-warfarin which will produce a comparable degree of anticoagulation. No such predictability is evident with respect to R(+)-warfarin. The slopes of the log plasma concentration-anticoagulant effect curves for R(+)-and S(-)-warfarin differ significantly. Therefore, the potency ratio of these enantiomers is dose-and concentration-dependent.

Adult↗
PubMed1978

Frequency distribution of bilirubin intrinsic clearance in adult male sprague--dawley rats.

The intrinsic body clearance of bilirubin was determined in 48 adult male Sprague--Dawley rats that received an intravenous infusion of bilirubin. The intrinsic body clearance was calculated from the infusion rate, the steady-state plasma concentration of total (free and protein-bound) bilirubin, and the free fraction of bilirubin in plasma. The intrinsic body clearance of bilirubin ranged from 5.05 to 13.20 liters/kg/min and was bimodally distributed, with half of the animals in each group. The plasma free fraction of bilirubin ranged from 0.00025 to 0.00077 (mean 0.00053) in the 24 intrinsically rapid metabolizers of bilirubin and from 0.00048 to 0.00103 (mean 0.00075) in the intrinsically slow metabolizers of the pigment. Thus, interindividual differences in the total clearance of bilirubin in the rats are due to differences in both intrinsic body clearance and plasma protein binding.

Animals↗
PubMed1978

Comparative pharmacokinetics of coumarin anticoagulants XXXIII: frequency distribution of dicumarol total clearance in rats.

The total clearance of dicumarol was determined in 172 adult male Sprague-Dawley rats. Clearance values ranged from 1.46 to 27.0 ml/hr/kg. Statistical analysis of a histogram of the total clearance values indicated a trimodal distribution, with modes at 6.28, 14.8, and 23.7 ml/hr/kg. The percentage of animals in each of these components was 60.5, 33.7, and 5.8. A previous study had shown that the total clearance of dicumarol was proportional to the fraction of nonprotein-bound drug in serum (serum free fraction) and that interindividual differences in total clearance of dicumarol in rats were due almost entirely to corresponding differences in the serum free fraction. Therefore, it is likely that the observed trimodal frequency distribution of total clearance values reflects a similar distribution of serum free fraction values of dicumarol. The frequency distribution curve for dicumarol total clearance is very similar to the trimodal frequency distribution curve for warfarin serum free fraction values in rats. This observation is consistent with the previously demonstrated strong correlation of serum free fraction values of dicumarol and warfarin in individual animals.

Animals↗
PubMed1978

Comparative pharmacokinetics of coumarin anticoagulants XXXV: Examination of possible pharmacokinetic interaction between (R)-(+)- and (S)-(--)-warfarin in humans.

The elimination kinetics and anticoagulant effect produced by single 1.5-mg/kg doses of (R)-(+(-, (S)-(--)-, and racemic warfarin were determined in 10 healthy men. The results obtained in experiments with the individual enantiomers were used to predict the elimination kinetics and anticoagulant effect of racemic warfarin, assuming that there is no interaction between the two enantiomers. These predictions were compared to experimental results, and no significant differences were observed. This finding suggests that there are no pronounced pharmacokinetic or pharmacodynamic interactions between single large doses of (R)-(+)- and (S)-(--)-warfarin in humans.

Adult↗
PubMed1978

[Thrombolysis: biochemical basis of fibrinolysis. Fibrinogen].

Fibrinogen is synthetised in the parenchymatous cells of the liver. It is broken down in the plasma by cells equipped with the appropriate enzymes. The fibrinogen molecule is a dimer with a molecular weight of 340,000. Each monomer consists of three polypeptidie chains (alpha A, beta B and gamma) joined by disulphide bridges. The N-terminal region is rigid and constitutes the N-DSK (N-disulphide knot) around which the three C-terminal free extremities are rolled, thereby giving a symmetry and spherical form to the molecule. The existence of several types of alpha A chains explains their important role in polymerisation.

Amino Acid Sequence↗
PubMed1978

[Action of proteolytic enzymes on fibrinogen].

The principal substrate of protealytic enzymes is fibrinogen. Thrombin severs four ARG-GLY bonds in the alpha A and beta B chains of its molecule, on the side of the terminal-N. It thus liberates two fibrinopeptides A and B, and leads to the formation of fibrin. Plasmin, by contrast, acts upon the fibrinogen molecule first by hydrolysis of the alpha and beta chains liberating the X fragment and three peptides A, B and C. It continues on the alpha, beta and gamma chains of fragment X, leading to the appearance of fragments Y and D. Fragment Y is in turn hydrolysed into a second fragment D and fragment E. The initial (X and Y) or terminal (D and E) fibrinogen breakdown products each possess their own anticoagulant properties together with immunological properties which may be used in their estimation.

Fibrin Fibrinogen Degradation Products↗
PubMed1978

[Enzymatic fibrinolytic agents].

Urokinase (UK) and streptokinase (SK) transform plasminogen into plasmin by rupture of a ARG-VAL bond and the liberation of a peptide with a molecular weight of 6000 to 8000. Urokinase is a physiological activator with a direct action. By contrast, streptokinase is an enzyme of bacterial origin and two hypotheses may be advanced to explain its mechanism of action: the formation of a SK-plasminogen complex capable of activatiing new molecules of plasminogen or the formation of a SK-plasminogen complex within which plasminogen is transformed to plasmin.

Endopeptidases↗
PubMed1978

[Fibrinolysis].

A large number of methods may be used in the study of fibrinolysis. They are either so-called direct when they demonstrate abnormal lytic activity and indirect when they analyse the results of this activity. In practical terms, the examinations used most widely are the euglobulin lysis test, evaluation of the plasminogenplasmin pair, and estimations of fibrinogen and of its breakdown products.

Blood Coagulation Tests↗
PubMed1978

Use of a programmable calculator to determine steady-state levels of drugs eliminated by parallel first-order and Michaelis-Menten kinetics.

A programmable calculator procedure for the determination of steady-state levels of drugs eliminated by one or more apparent first-order plus one or two Michaelis-Menten processes in parallel is described. The differential expression for this pharmacokinetic system was converted to a reduced cubic equation suitable for calculators with trigonometric functions. A detailed program description and user instructions are presented. Steady-state levels of salicylic acid as a function of dosing rate were calculated to illustrate use of the program in clinical pharmacokinetics. The calculator program provides a facile and rapid means of determining the effect of changes in dosing rate, bioavailability and elimination constants on steady-state levels of salicylic acid and certain other drugs with nonlinear elimination characteristics.

Adult↗
PubMed1978

Clinical pharmacokinetics of aspirin.

Aspirin is very rapidly absorbed from the gastrointestinal tract when administered as a solution, and somewhat more slowly when administered in tablets. It is rapidly hydrolyzed in the body to salicylic acid; the plasma concentration of the latter must be maintained within a relatively narrow range to obtain an adequate anti-inflammatory effect and to minimize systemic adverse effects. The two major pathways of salicylate elimination, i.e., formation of salicyluric acid and salicyl phenolic glucuronide, become saturated at relatively low body levels of the drug. Consequently, steady-state ("plateau") salicylate levels increase more than proportionately with increasing daily dose, and the time required to reach steady state increases with increasing daily dose. The renal clearance of salicylic acid increases markedly with increasing urine pH; antacids capable of increasing urine pH can therefore cause a pronounced lowering of steady-state salicylate concentrations under clinical conditions. There are pronounced intersubject differences in salicylate elimination kinetics; dosage must be individualized on the basis of plasma concentration and clinical response. The drug is readily transferred across the placenta and is only slowly eliminated by the newborn infant. The drug is also transferred from mother to nursing infant through the breast milk.

Absorption↗