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Biomedical subjects

E Jähnchen

Publications and source records attributed to E Jähnchen.

At least 19 recordsLinked to original sources
PubMed1979

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

The interaction of phenylbutazone with the enantiomers and racemic [3H]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 microgram/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 nearly unaffected by phenylbutazone. Thus there is no evidence for a stereoselective drug interaction between phenprocoumon and phenylbutazone. For racemic [oH]phenprocoumon it was possible to follow the kinetics of free drug in plasma and liver along with the time course of anticoagulant activity. In these studies, free drug concentrations in plasma and liver increased during treatment with phenylbutazone, but the elimination rate constant of free racemic phenprocoumon in plasma and liver remained essentially unchanged. Phenylbutazone markedly decreased the volume of distribution referenced to free drug and the clearance of free phenprocoumon (i.e., intrinsic metabolic clearance). Whereas the total (bound and unbound) drug concentration--effect relationship in plasma and liver was shifted to the left in rats treated with phenylbutazone, such shift was not seen in the free drug concentration--response relationship. In conclusion, the increase in the free concentration of phenprocoumon in plasma and liver and the concomitant decrease in the clearance of free drug are the mechanisms responsible for the marked and sustained enhancement of the anticoagulant effect which follows treatment with phenbutazone.

4-Hydroxycoumarins↗
PubMed1979

Pharmacokinetics of azapropazone following single oral and intravenous doses.

The pharmacokinetics of azapropazone (Prolixan) was studied in 7 healthy volunters following single oral and i.v. doses of 600 mg. After i.v. injection plasma concentration declined biexponentially with time. The half-life of the beta-phase was 13.6 +/- 2.6 h (mean +/- SD), the apparent volume of distribution 11.9 +/- 3.5 l, and the total clearance 10.1 +/- 2.1 ml . min-1. Following oral administration peak plasma concentrations occurred between 3 and 6 h and declined with a beta-phase half-life of 14.3 +/- 2.8 h. The binding of azapropazone to plasma proteins was high (ranging from 99.52 to 99.67% at a total plasma concentration of 75 micrograms/ml). The bioavailability of azapropazone when administered as capsules was 83 +/- 19%.

Administration, Oral↗
PubMed1978

Enhanced elimination of warfarin during treatment with cholestyramine.

1 The elimination and anticoagulant activity of a single intravenous dose of warfarin (1.0-1.2 mg/kg) without and with concomitant cholestyramine treatment (about 4 g three times daily) was studied in five healthy male subjects. 2 Cholestyramine treatment decreased the biological half-life of plasma warfarin (from a mean value of 2 days -1.3 days) and increased the total clearance of this drug (from a mean value of 37 ml kg-1 day-1--53 ml kg--1 day--1). 3 The total anticoagulant effect per dose of warfarin, as measured by the area under the effect v time curve, was also reduced by cholestyramine (average reduction of about 25%). 4 Warfarin possibly undergoes enterohepatic recycling in man which can be interrupted by cholestyramine.

Adult↗
PubMed1977

Interaction of allopurinol with phenprocoumon in man.

Conditions in two patients on long-term phenprocoumon (Marcumar) treatment are reported who had signs of phenprocoumon overdosage when given simultaneously allopurinol. The determination of phenprocoumon plasma concentrations in one patient showed that phenprocoumon accumulates for several weeks during treatment with allopurinol. Signs of phenprocoumon overdisage thus can appear long time after starting allopurinol treatment.

4-Hydroxycoumarins↗
PubMed1977

Interruption of the enterohepatic circulation of phenprocoumon by cholestyramine.

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 that phenprocoumon undergoes extensive enterohepatic recycling in man which can be effectively interrupted by cholestyramine.

4-Hydroxycoumarins↗
PubMed1977

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

The elimination, distribution and anticoagulant activity of S(-)-, R(+)-, and R,S(+/-)- phenoprocoumon 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(+)-phenprocouman. 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 for the R(+)-enantiomer (5-2). At a total concentration of 16-8 microgram ml-1 the percentage of unbound drug in rat serum was significantly higher for the S(-)- (1-13%) than that for the R(+)-enantiomer (0.76%). Values obtained for the racemate were always between those of the enantiomers. It is concluded that stereoselective differences in the distribution between plasma and liver, and consequently in the rate of elimination are most likely due to stereoselective differences in serum protein binding. The greater anticoagulant potency of the S(-)- over the R(+)-enantiomer, cannot be explained primarily by the observed pharmacokinetic differences.

4-Hydroxycoumarins↗
PubMed1977

[Pharmacokinetic aspects of overdosage and intoxication with oral anticoagulant drugs (author's transl)].

Three aspects of treatment with oral anticoagulant drugs are discussed: 1. Drug interactions which can lead to changes in the elimination or distribution of oral anticoagulant drugs with special emphasis on the time course of the augmentation of the anticoagulant effect. 2. Pharmacokinetic factors responsible for inter- and intrasubject differences in the response to oral anticoagulant drugs. 3. Treatment of overdosage and intoxication with oral anticoagulant drugs. Besides symptomatic treatment with vitamin K and prothrombin complex concentrate the interruption of the enterohepatic recycling by cholestyramine is demonstrated as a useful method for enhancing the elimination of phenprocoumon and warfarin from the body.

Administration, Oral↗