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Biomedical subjects

H J Gilfrich

Publications and source records attributed to H J Gilfrich.

At least 55 records · Page 3Linked to original sources
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

[Intestinal absorption of digoxin in systemic sclerosis (author's transl)].

Gastro-intestinal absorption of digoxin was evaluated in 18 patients with progressive systemic sclerosis. In 8 patients a single-dose crossover study was performed after oral and intravenous administration of 0.5 mg digoxin by comparing the aera under the eight-hour plasma concentration curve. The fraction of the dose absorbed was diminished in 4 patients to less than 55%. There was a significant positive correlation between the extent of digoxin absorption and xylose renal excretion. In addition, steady state digoxin plasma levels and 24-h urinary excretion of digoxin were determined during maintenance therapy in 12 patients. In 6 patients renal excretion of digoxin was clearly less than in normal subjects during chronic dosing of the same digoxin preparation. This finding corresponded well with digoxin plasma levels below the usual therapeutic range in most of the patients. The impaired absorption of digoxin failed to correlate with the extent of the skin manifestation or the time course of the disease while there was massive oesophageal dysfunction in most of these patients. The results suggest that an inadequate therapeutic response to cardiac glycosides in patients suffering from progressive systemic sclerosis is at least partially due to impaired digoxin absorption. Similar problems could occur in therapy of the disease itself due to insufficient enteral absorption of drugs used in treatment of systemic sclerosis.

Administration, Oral↗
PubMed1977

[Clinical and pharmacokinetic studies in patients with digitalis intoxication (author's transl)].

6 patients with severe digitalis intoxication were studied while hospitalised in a coronary care unit. 2 and 4 patients had ingested high doses of lanatosid C and digoxin, respectively. In three cases ventricular arrhythmias, in one of these and two further cases SA blocking and an additional A-V-block in one case were observed. Maximum blood levels of digoxin between 3.4 and 20 ng/ml were determined several hours after the ingestion. The maximal blood levels were achieved in one patient only 52 h after ingesting lanatosid C and in one patient taking digoxin after 12.5 h. Potassium concentrations in plasma were elevated in 4 patients. Antiarrhythmic and electrolyte therapy is discussed and the usefulness of a stomach lavage for diminishing the quantity of absorbed lanatosid C is shown in one patient who had a maximal blood level of 3.4 ng/ml after taking 23.7 mg of lanatosid C. Cumulative urinary excretion of this patient was 0.68 mg within 5.5 days. This result confirms the minimal enteral absorption under the therapy chosen.

Adult↗
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

[Kinetics of digitoxin during antirheumatic therapy with azapropazone (author's transl)].

The effect of chronic therapy with 5-dimethylamino-9-methylamino-9-methyl-2-propyl-1H-pyrazolo[1,2-a] [1,2,4] benzotriazine-1,3-(2H)-dione-dihydrate (azapropazone-dihydrate; Prolixan 300) on the elimination of a single i.v. dose of digitoxin was studied in 8 patients with rheumatoid arthritis and osteoarthritis using a crossover design. 0.5 mg digitoxin were injected i.v. alone and together with a chronic oral therapy of azapropazone starting 3 weeks before digitoxin was given. Digitoxin plasma levels were determined by radioimmunoassay over a period of 19 days. The half-life for plasma digitoxin was 6.4 +/- 0.5 days after digitoxin alone and 7.0 +/- 0.6 days during azapropazone treatment. In two patients the half-life of digitoxin was increased by about one-third during azapropazone therapy. The areas under the plasma digitoxin curve were 2592 +/- 262 ng/ml X h and 2615 +/- 273 ng/ml X h, respectively. None of the differences were statistically significant. It was concluded that there was no clinically significant interaction between azapropazone and a single dose of digitoxin.

Adult↗
PubMed1976

Pharmacokinetic analysis of the interaction between dicoumarol and tolbutamide in man.

The effect of repeated administration of tolbutamide on the elimination and anticoagulant action of a single oral dose of dicoumarol 600 mg was studied in four healthy male subjects using a crossover design. In all subjects the plasma concentration of dicoumarol in the postabsorptive phase was lower during concomitant tolbutamide treatment. However, the subjects differed with respect to the elimination kinetics of dicoumarol and the effect of tolbutamide on some of the measured pharmacokinetic paramaters. In two subjects dicoumarol was eliminated by apparent first-order kinetics. Tolbutamide led to a pronounced increase in the elimination rate and a shift in the plasma concentration-response relationship towards a lower concentration of dicoumarol. The total hypoprothrombinaemic effect per dose of dicoumarol was not affected. The decline in the dicoumarol concentration in plasma in the other two subjects was concentration-dependent. Apparent first-order kinetics were observed only at plasma concentrations below 10 mg/L. Tolbutamide treatment did not markedly affect the slope of the terminal portion of the plasma concentration vs. time curve, but diminished the area under the total curve. The plasma concentration-response relationship of dicoumarol was not affected by tolbutamide, but there was a small decrease in the area under the anticoagulant effect vs. time curve. The plateau level of tolbutamide in plasma increased considerable in all subjects after administration of one dose of dicoumarol. Thus, simultaneous administration of tolbutamide and dicoumarol to man often causes no changes in the anticoagulant activity of dicoumarol, but this is due not to lack of interaction of the drugs but to the complexity of their interactions, involving processes that may counteract each other.

Adult↗
PubMed1976

The enantiomers of phenprocoumon: pharmacodynamic and pharmacokinetic studies.

The pharmacodynamics and pharmacokinetics of the optical enantiomers of phenprocoumon were studied in 5 normal subjects and compared to the racemic mixture. Each subject received a single oral dose of 0.6 mg/kg of racemic, S(-), and R(+) phenprocoumon. S(-) phenprocoumon was 1.6 to 2.6 times as a potent as R(+) phenprocoumon when the area under the effect/time curve was used to quantify the total anticoagulant effect per dose. Comparing the plasma concentrations that elicited the same anticoagulant effect, S(-) phenprocoumon was 1.5 to 2.5 times as potent as R(+) phenprocoumon. The anticoagulant activity of the racemic mixture was between that of the enantiomers. There was no distinct difference in the rate of elimination between the enantiomers. The apparent volume of distribution and the plasma clearance for S(-) phenprocoumon were less than those for R(+) phenprocoumon. When the binding of the enantiomers to human serum albumin was compared, S(-) phenprocoumon was more highly bound than R(+) phenprocoumon. The protein binding of racemic phenprocoumon was between that of the enantiomers. The results show that S(-) phenprocoumon is more potent anticoagulant than R(+) phenprocoumon and that the pharmacokinetic differences between the enantiomers are due mainly to differences in their distribution.

Adult↗