Search results for "4-Hydroxycoumarins"

Interruption of the enterohepatic circulation of phenprocoumon by cholestyramine

1977

The effect of cholestyramine (12 gm/day divided into 3 doses) on the pharmacokinetics and pharmacodynamics of a single intravenouse dose (30 mg) of phenprocoumon was studied in 6 normal subjects. Cholestyramine treatment led to an increase in the rate of elimination of phenprocoumon in all. Total clearance increased 1.5- to 2-fold. The total anticoagulant effect per dose was considerably reduced during treatment with cholestyramine. Binding studies in vitro showed that phenprocoumon is strongly bound to cholestyramine and that at a given cholestyramine concentration the percentage of phenprocoumon bound remained constant over a large concentration range of phenprocoumon. The results suggest…

Species-dependent stereospecific serum protein binding of the oral anticoagulant drug phenprocoumon

1978

13 mammalian species are classified into 3 clearcut groups with respect to the stereospecific serum protein-binding of phenprocoumon: 2 groups showing opposed stereospecific binding characteristics and a 3rd group exhibiting no stereospecific binding. Structural differences in the albumin molecule account for these stereospecific differences in serum protein-binding.

Mediterranean Diet Decreases the Initiation of Use of Vitamin K Epoxide Reductase Inhibitors and Their Associated Cardiovascular Risk: A Randomized C…

2020

Our aim is to assess whether following a Mediterranean Diet (MedDiet) decreases the risk of initiating antithrombotic therapies and the cardiovascular risk associated with its use in older individuals at high cardiovascular risk. We evaluate whether participants of the PREvenci&oacute

Effect of serum protein binding on pharmacokinetics and anticoagulant activity of phenprocoumon in rats.

1980

The relationship among serum protein binding, kinetics of elimination, distribution, and anticoagulant activity of phenprocoumon was investigated in 25 selected outbred Sprague-Dawley rats which differed in the extent of serum protein binding of this drug. In addition, the serum protein binding of phenprocoumon was altered in inbred Lewis rats by continuous treatment with tolbutamide. This drug was found to displace phenprocoumon from serum proteins without affecting its intrinsic clearance. The serum free fraction values (fs)of the selected Sprague-Dawley rats ranged from 0.0053 to 0.0145. There were positive and linear correlations between fsand the first-order elimination rate constant (…

Rapid gas chromatographic determination of underivatized phenprocoumon in plasma.

1977

Interaction of phenylbutazone with racemic phenprocoumon and its enantiomers in rats.

1979

The interaction of phenylbutazone with the enantiomers and racemic [ 3 H]phenprocoumon was studied in male inbred Wistar-Lewis rats following a single i.v. dose of the three forms of phenprocoumon and chronic oral treatment with phenylbutazone (average plasma concentration of about 60 Μg/ml). Phenylbutazone augmented the anticoagulant effect of R(+), S(−), and R, S (±) phenprocoumon to a similar extent. The free fraction of drug in the plasma of the enantiomers and racemic phenprocoumon increased in the presence of phenylbutazone. However, the rate of elimination of total drug from plasma and liver and the distribution between liver and plasma of all three forms of phenprocoumon remained ne…

Stereoselective drug distribution and anticoagulant potency of the enantiomers of phenprocoumon in rats

1977

Abstract The elimination, distribution and anticoagulant activity of S(—)-, R(+)-, and R,S(±)-phenprocoumon were determined in male Wistar-Lewis rats after intravenous injection of a single dose of 0·6 mg kg−1. From the plasma concentrations which elicited the same anticoagulant effect, S(—)-phenprocoumon was 4 to 5 times more potent than R(+)-phenprocoumon. The potency of the racemate was between those of the enantiomers. The mean biologic half-life of the S(—)-enantiomer was shorter (12·5 h) than that of R(+)-phenprocoumon (17·8 h). No differences were observed in the apparent volume of distribution. However, the mean liver: plasma concentration ratio was higher for the S(—)-(6·9) than fo…

Dose-dependent metabolism and hepatic distribution of phenprocoumon in rats

1988

The dose-dependency of phenprocoumon disposition was determined in rats by iv administration of 0.1 and 1.0 mg/kg doses to separate groups of animals. The intrinsic clearance (unbound clearance) was 33% lower in the animals given 1.0 mg/kg dose than in the animals given 0.1 mg/kg dose. The apparent unbound volume of distribution was 55% lower and the elimination rate constant 54% higher in the high dose group than in the lower dose group. Binding of phenprocoumon to liver showed saturability with a two- to threefold higher apparent unbound fraction of phenprocoumon in liver in animals given the high dose in comparison to animals given the low dose.

Factors responsible for interindividual differences in the dose requirement of phenprocoumon

1987

The total and unbound plasma concentrations of phenprocoumon and the prothrombin complex activity were determined in 51 patients on phenprocoumon. A 7-fold difference in the dosing rate (10-70 micrograms/kg/day) was required to maintain the prothrombin complex activity at 11-30% of normal. The variation in dosing requirement was mainly due to interindividual differences in the intrinsic clearance of phenprocoumon and only to a minor degree to differences in sensitivity to it. On average patients with myocardial infarction required only 2/3 of the daily dose of phenprocoumon of post cardiac surgery patients and patients with thrombosis and emboli. That difference appeared to be due to higher…

Sex-related Differences in Disposition and Response to Phenprocoumon in Rats

1988

Abstract The pharmacokinetics and the pharmacological response to phenprocoumon have been studied in female and male inbred Lewis-Wistar rats. A significantly lower clearance was found in female than in male rats (7.9 ± 1.4 vs 24.5 ± 2.5 mL h−1 kg−1, respectively; t = 15.09, P < 0.001) as well as a lower apparent volume of distribution (288 ± 46 vs 617 ± 105 mL kg−1; t = 7.58, P < 0.001) and a longer half-life (25.5 ± 3.4 vs 17.5 ± 1.8 h; t = 5.16, P < 0.001). The binding of phenprocoumon was higher in female than in male rats (fu: 0.0096 ± 0.0008 vs 0.0124 ± 0.0007, respectively; t = 6.66, P < 0.001). The total (C) as well as the unbound concentration (Cu) neede…