Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Phenprocoumon”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 73 records · Page 4Linked to original sources
PubMed1987

The effect of sulfinpyrazone on the disposition of pseudoracemic phenprocoumon in humans.

The effect of sulfinpyrazone on the pharmacokinetics and disposition of the enantiomers of pseudoracemic phenprocoumon was assessed by analyzing serial plasma, urine, and fecal samples for parent drug and metabolites by GC/MS. Essentially all of the administered dose could be accounted for either as parent drug, known metabolites, or their conjugates. Phenprocoumon and the 7-hydroxymetabolite represented the major materials recovered. All drug-related materials excreted into the urine were extensively conjugated. Sulfinpyrazone treatment did not affect the hypoprothrombinemia produced by phenprocoumon nor did it significantly alter the plasma elimination kinetics of the individual (R)- and (S)-enantiomers. However, an apparent increased free fraction of both enantiomers in plasma and inhibition of 7-hydroxylation of (S)-phenprocoumon were observed in the presence of sulfinpyrazone. The results of this study are contrasted with those of a previous study on the interaction between sulfinpyrazone and the structurally similar coumarin anticoagulant warfarin.

4-Hydroxycoumarins↗
PubMed1979

[Interaction of rifampicin with phenprocoumon (author's transl)].

Prothrombin time and plasma phenprocoumon levels were serially controlled, at short intervals, in three tubercular patients receiving both tuberculostatic drugs and phenprocoumon. The required phenprocoumon dose was continuously adapted to the prothrombin time values. During and after treatment with rifampicin optimal levels of prothrombin time were difficult or even impossible to achieve in two of the three patients. This confirms the known loss of effectiveness of the coumarins induced by rifampicin. This action has a slower onset and disappears more gradually than after acenocoumarol or warfarin. It is, therefore, likely that these two latter drugs are more suitable in patients treated with rifampicin than phenprocoumon.

4-Hydroxycoumarins↗
PubMed1999

[Skin necrosis in the front foot area during anticoagulation with phenprocoumon].

HISTORY AND ADMISSION FINDINGS: A 52-year-old woman was admitted because of pain for several days in the lower left leg and increasing pretibial swelling with livid discoloration. Six months before she had undergone a bilateral adnexectomy with removal of the omentum and subsequent chemotherapy for ovarian cancer. INVESTIGATIONS: Duplex sonography on the day of admission revealed thrombosis of the left popliteal vein with an unobstructed femoral vein. Both the quick value (89%) and partial thromboplastin time (PTT, 35.9 s) were within normal limits. Computed tomography and sonography were highly suspicious of a local recurrence of the ovarian cancer with peritoneal carcinomatosis. TREATMENT AND COURSE: PTT-effective heparinization (heparin-Na) was initiated together with overlapping anticoagulation with phenprocoumon (thromboplastin time 20-30%). On the 9th day after starting phenprocoumon painful, black necrotic changes began to appear on the skin of the left first to fourth toes. Assuming these to be due to phenprocoumon, anticoagulation was switched to low-molecular heparin (Enoxaparin), and antithrombin III and protein C were administered. A few days later thrombosis of the right iliac vein occurred, probably caused by local recurrence of the ovarian cancer. No palliative chemotherapy was undertaken in view of the thrombotic complications. The patient died a few months later from the cancer. CONCLUSION: If there is an underlying malignancy, chemotherapy and therapeutic vitamin-K antagonism in the presence of thromboembolic complications increases the risk of lowering protein C activity and may cause the rare complication of skin necrosis, induced by phenprocoumon.

Anticoagulants↗
PubMed2001

Idiosyncratic drug allergic phenprocoumon-induced hepatitis with subacute liver failure initially misdiagnosed as autoimmune hepatitis.

BACKGROUND: Coumarin anticoagulants are known to cause hepatotoxicity, but only a few cases have been reported. Coumarins are usually administered following cardiovascular surgery and the differential diagnosis is post-transfusion hepatitis. METHODS: We report the case of a 46-year-old woman who presented with jaundice, elevated liver function tests, positive antinuclear and smooth muscle antibodies following prodromal signs of fatigue and nausea. The patient had been treated with phenprocoumon for 5 months in order to prevent thromboembolism after two strokes assumed to be due to an open foramen ovale and an aneurysmatic atrial septum. RESULTS: There was no evidence of viral or other causes of hepatitis. The patient rapidly developed subacute liver failure with encephalopathy and phenprocoumon treatment was stopped. With intensive care support, as well as high-dose prednisolone treatment, she recovered. Owing to positive antinuclear and smooth muscle antibodies, the initial diagnosis 'acute autoimmune hepatitis with liver failure was made. CONCLUSION: The lack of hypergammaglobulinaemia and the rapid recurrence of hepatitis following re-exposure to phenprocoumon led to the final diagnosis of phenprocoumon-induced idiosyncratic drug allergic hepatitis with secondary autoimmune phenomena.

Anti-Inflammatory Agents↗
PubMed1995

Randomized comparison of aspirin and phenprocoumon for prevention of right-sided thromboembolic complications associated with transvenous defibrillation leads.

Death due to pulmonary embolism caused by thrombosis formation along a pacing wire has been reported in patients with antibradycardia pacemakers. The purpose of this prospective and randomized study was to evaluate the effects of prophylactically assigned aspirin (100 mg per day) or phenprocoumon (a coumarin derivative) on the incidence of right-sided thromboembolic complications associated with transvenous defibrillation leads. Multiplane transoesophageal echocardiography and pulmonary scintigraphy were performed in 62 consecutive patients immediately and 6 +/- 2 months after transvenous defibrillator implantation. Aspirin or phenprocoumon was administered to the patients in a randomized and parallel manner. By means of multiplane transoesophageal echocardiography and pulmonary scintigraphy no thromboembolic events were observed immediately after transvenous defibrillator implantation. After 6 +/- 2 months, however, multiplane transoesophageal echocardiography disclosed thrombi on the transvenous leads in 13 of 62 patients (21%) despite antithrombotic therapy. At the same time, pulmonary scintigraphy did not reveal any defects compatible with pulmonary embolism. Although thrombi occurred in only four patients treated with phenprocoumon, but in nine patients receiving aspirin, this difference was statistically insignificant. Other variables associated with the occurrence of thrombosis formation were not identified. One fatal intracranial haemorrhage occurred in the phenprocoumon group.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed2004

The risk of overanticoagulation in patients with cytochrome P450 CYP2C9*2 or CYP2C9*3 alleles on acenocoumarol or phenprocoumon.

Cytochrome P4502C9 (CYP2C9) is the main enzyme implicated in coumarin anticoagulant metabolism. The variant alleles CYP2C9*2 and CYP2C9*3 are associated with an increased response to warfarin. However, an effect on acenocoumarol dose requirements appears to be absent for the CYP2C9*2 allele and the consequences for the metabolism of phenprocoumon have not yet been established. We investigated CYP2C9 polymorphisms in relation to the international normalized ratio (INR) during the first 6 weeks of treatment and its effect on the maintenance dose in a cohort of 1124 patients from the Rotterdam Study who were treated with acenocoumarol or phenprocoumon. There was a statistically significant difference in first INR between patients with variant genotypes and those with the wild-type. Almost all acenocoumarol-treated patients with a variant genotype had a significantly higher mean INR and had a higher risk of an INR > or = 6.0 during the first 6 weeks of treatment. A clear genotype-dose relationship was found for acenocoumarol-treated patients. For patients on phenprocoumon, no significant differences were found between variant genotypes and the wild-type genotype. Individuals with one or more CYP2C9*2 or CYP2C9*3 allele(s) require a significantly lower dose of acenocoumarol compared to wild-type patients. Phenprocoumon appears to be a clinically useful alternative in patients carrying the CYP2C9*2 and *3 alleles.

Acenocoumarol↗
PubMed1989

Lack of effect of acitretin on the hypothrombinemic action of phenprocoumon in healthy volunteers.

A possible influence of the aromatic retinoid acitretin on the hypothrombinemic action of phenprocoumon was investigated in 10 healthy male volunteers, 22-33 years of age. In a run-in period of 17 days the prothrombin complex activity (Quick) of the subjects was adjusted by individual doses of phenprocoumon (range 1.5-3 mg/day) to a therapeutic level of around 20% (INR = 3.6). Afterwards the dosage regimens were kept unchanged until day 40 when 60 mg oral vitamin K1 were administered. From day 18 to day 28 once daily doses of 50 mg acitretin were applied concurrently with phenprocoumon. The mean (+/- SD) prothrombin complex activity increased slightly and steadily from 19 +/- 1% on day 10 over 22 +/- 1% on day 18 to 24 +/- 4% on day 28 and reached 27 +/- 4% on day 38 (the corresponding INRs were 3.30, 2.91, 2.71 and 2.46 respectively). There were, however, no relevant changes of the Quick values in any subject which could be attributed to acitretin. It can be concluded that, under the present experimental conditions, acitretin did not affect significantly the anticoagulant action of phenprocoumon.

4-Hydroxycoumarins↗
PubMed2003

Comparison of control and stability of oral anticoagulant therapy using acenocoumarol versus phenprocoumon.

Variability in the control of oral anticoagulant therapy has been associated with a heightened risk of complications. We compared control of anticoagulation between two commonly used coumarins, phenprocoumon and acenocoumarol, and among anticoagulation clinics. All qualifying patients were managed at six regional anticoagulation clinics in the Netherlands. This retrospective cohort study compiled data during a three-year period from a computerised dosing and management system. Anticoagulation control was expressed as the percent of time within the therapeutic range and stability expressed as the time-weighted variance in the international normalised ratio (INR). Data were available for 22,178 patients of whom 72% were treated with acenocoumarol. INRs of patients who received phenprocoumon were within the therapeutic range 50% of the time compared with 43% for acenocoumarol (OR 1.32, 95% CI 1.24-1.41). Moreover, patients on phenprocoumon required 15% fewer monitoring visits and had more stable INR values. These observations were consistent for all six clinics. There were also sizable differences between the clinics with respect to control and stability of anticoagulation that were stable from year-to-year and were unrelated to the drug used. With its longer half-life of three to five days, phenprocoumon produces more stable anticoagulation than acenocoumarol and should generally be the drug of choice when these are the available choices. The differences observed among clinics suggest that certain clinics employ policies and practices resulting in better control of anticoagulation.

Acenocoumarol↗
PubMed2001

Drug interaction: omeprazole and phenprocoumon.

BACKGROUND: Oral anticoagulants like the coumarin derivatives are characterised by a particularly narrow therapeutic range. Any interfering co-medication can pose a challenge to establishing a stable anticoagulant dosage regimen and thus present a serious risk for the patient. Here we describe two cases of patients on anticoagulant therapy that suggest possible drug interactions between phenprocoumon and the proton pump inhibitor omeprazole. RESULTS: In both patients, the International Normalised Ratio (INR) increased beyond the therapeutic range after they were given omeprazole for the treatment of gastrointestinal symptoms. The INR returned to therapeutic levels after the phenprocoumon dose was reduced (Case 1) and omeprazole discontinued (Case 2). CONCLUSIONS: The increased anticoagulant activity of phenprocoumon observed in the two described cases and the known interaction potential of omeprazole suggest that the clearance of phenprocoumon may have been reduced due to competitive inhibition of its degradation by omeprazole. Drug interactions may be one of the reasons for the difficulties encountered with some patients in establishing a stable anticoagulant therapy. Physicians should carefully review any concurrently used medication and if possible opt for drugs with a low interaction potential.

Aged↗
PubMed1988

Decreased serum osteocalcin levels in phenprocoumon-treated patients.

Osteocalcin (OC) is a noncollagenous bone matrix protein containing gamma-carboxyglutamic acid, the synthesis of which is vitamin K dependent. Serum OC levels are generally believed to reflect the de novo synthesis of OC by osteoblasts and thus reflect bone formation. We measured serum OC levels by RIA in 48 patients receiving phenprocoumon anticoagulant treatment, which inhibits the posttranscriptional synthesis of gamma-carboxyglutamic acid, and in 22 matched normal subjects. The median serum OC level in the patients receiving phenprocoumon therapy was significantly lower than that in the normal subjects (P less than 0.0001). In 27 patients receiving anticoagulant therapy and in 21 normal subjects the proportion of noncarboxylated OC to total OC also was determined. The proportion of OC that was noncarboxylated was significantly higher in the patients receiving phenprocoumon therapy than in the normal subjects (P less than 0.0001). We conclude that OC carboxylation is impaired in patients receiving oral anticoagulant therapy. The decreased total OC levels in patients receiving phenprocoumon treatment might result from decreased bone formation, although these patients do not have symptoms of bone disease.

4-Hydroxycoumarins↗
PubMed1989

Absence of interaction between ramipril, a new ACE-inhibitor, and phenprocoumon, an anticoagulant agent.

In a double-blind, placebo-controlled crossover trial, the effects of ramipril, a long-acting non-sulphydryl angiotensin I converting enzyme inhibitor, on phenprocoumon steady-state pharmacodynamics were investigated in 8 healthy male volunteers taking individually fixed doses of phenprocoumon. The results showed that 5 mg ramipril or placebo once daily for 7 days did not alter the anticoagulant response (Quick values) to phenprocoumon after a stabilization phase of 2 weeks. Mean Quick values during the steady-state phase with ramipril and placebo were 67.5% and 69.3%, respectively. The clotting factors II, VII, IX and X as well as protein C decreased in the run-in phase and remained stable both during ramipril and placebo treatment. There were no differences between ramipril or placebo treatments. As the phenprocoumon dosage was kept unchanged during the double-blind phase, the results indicate that ramipril does not interfere with the vitamin K-dependent cascade.

4-Hydroxycoumarins↗
PubMed1975

Collaborative study of a semiautomated method for the analysis of acenocoumarol, phenprocoumon, and potassium warfarin tablets.

This collaborative study was undertaken to determine if the anticoagulants acenocoumarol, phenprocoumon, and potassium warfarin could be analyzed by the automated analysis system described in the collaborative study for the analysis of sodium warfarin and dicumarol. Collaborators were supplied with a composited tablet sample of each anticoagulant. Results agreed well with the National Formulary methods for phenprocoumon and potassium warfarin, and an unpublished method for acenocoumarol. For acenocoumarol, coefficients of variation on individual sets of data ranged from 0.30 to 1.94% For phenprocoumon, coefficients of variation ranged from 0.52 to 1.20%. For potassium warfarin, coefficients of variation ranged from 0.54 to 1.79%. The results of this study show that acenocoumarol, phenprocoumon, and potassium warfarin can be analyzed by the official AOAC method for the analysis of sodium warfarin and dicumarol tablets.

Acenocoumarol↗
PubMed1976

GLC determination of plasma concentrations of phenprocoumon.

A GLC method for the quantitative estimation of phenprocoumon from plasma is described. Plasma containing phenprocoumon, to which a known amount of phenytoin is added as the internal standard, is acidified and extracted with ethylene dichloride. The drug and the internal standard are then back-extracted into alkali, which is acidified and reextracted with ethylene dichloride. The organic extract is evaporated, and the evaporated residue is mixed with 50 mul of trimethylanilinium hydroxide in methanol. Aliquots (1-2 mul) are injected into a gas chromatography equipped with a flame-ionization detector in which the injection port is held at 325 degrees. The methyl derivatives of phenprocoumon and the internal standard give sharp, well-separated, symmetrical peaks. The method is of sufficient sensitivity to determine 0.125 mug/ml of the drug in plasma with a coefficient of variation of 7%.

Alkylating Agents↗
PubMed1977

Double blind study of the effect of glafenine (Glifanan) on oral anticoagulant therapy with phenprocoumon (Marcumar).

The interaction between phenprocoumon (Marcumar) and glafenine (Glifanan) was investigated in a double blind study of twenty patients receiving long term treatment with phenprocoumon. Thrombotesttime (TT) values had been stable for more than three months before the study. Patients taking glafenine showed a significant increase in TT during the second and third week of the trial (P less than 0.05) compared with the placebo group. tthe increase in TT was not significant in the fourth week. The average concentrations of phenprocoumon were similar in both groups, which suggests that displacement of the drug from binding was not important. Concentrations of clotting factors II, VII and X showed a decrease in all patients at the time of the maximum TT values. A possible explanation for this interaction is discussed, but the mechanism remains uncertain.

4-Hydroxycoumarins↗
PubMed1986

Phenprocoumon metabolites in human plasma; characterization by HPLC and GC-MS.

Pooled plasma from patients receiving phenprocoumon anticoagulant therapy was extracted and the following substances were characterized: phenprocoumon, and its 7-hydroxy,4'-hydroxy and 6-hydroxy derivatives; they were identified by HPLC and after methylation by quartz capillary GC-MS using the electron impact and selective ion monitoring modes. This is the first occasion when phenprocoumon metabolites have been identified in plasma; they were unconjugated and in much lower concentrations (43.2 and 2 ng/ml for the 7,4' and 6-hydroxy derivatives, respectively) than the original compound (2000 ng/ml).

4-Hydroxycoumarins↗
PubMed1978

Phenprocoumon requirement, whole blood coagulation time, bleeding time and plasma gamma-GT in patients receiving mianserin.

A possible interaction between the tetracyclic antidepressant mianserin and a coumarin derivative has been investigated. Sixty-three subjects, 61 of whom required anticoagulant therapy for a variety of medical conditions, were treated for 5 consecutive weeks with phenprocoumon, in a dose adjusted to reduce the prothrombin time to 15%-25%. After an initial control period of one week, subjects were randomly treated under double-blind conditions with mianserin 3 X 10 mg daily or 3 X 20 mg daily, or with a matching placebo. The dose of mianserin was gradually increased to reach the maximum by the 6th day. Three subjects dropped out and 60 completed the trial. The dose of phenprocoumon and the prothrombin, bleeding, and coagulation times were not significantly affected by administration of mianserin. It can be concluded that there is no clinically important interaction between phenprocoumon and doses of mianserin effective in depression. Sedation was more frequent in patients taking mianserin than in those given placebo.

4-Hydroxycoumarins↗
PubMed1988

Dose-dependent metabolism and hepatic distribution of phenprocoumon in rats.

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.

4-Hydroxycoumarins↗
PubMed2005

[Off-label use in long-term anticoagulation after liver transplantation due to phenprocoumon-induced hepatic failure].

BACKGROUND: Drug therapy should be individualized according to criteria of efficacy, adverse effects, and treatment adherence. This is particularly important at the interface of inpatient and ambulatory care. Aspects of drug approval (labeling) and individual refunding by health care insurance should also be taken into account. CASE REPORT: A patient (male, 61 years, painter) showed elevated transaminases after treatment with phenprocoumon because of a deep vein thrombosis in 1999. Transaminases normalized completely after discontinuation of phenprocoumon. Other reasons for the elevated transaminases could be excluded. After a recurrent thrombosis in 2003 phenprocoumon was prescribed again followed by recurrent elevation of transaminases and subsequent cholestatic hepatitis progressing to fulminant hepatic failure that required liver transplantation. After transplantation the patient's general state of health was good and liver function nearly normal. Anticoagulation was indicated beyond the postoperative phase because of recurrent deep vein thrombosis and atrial fibrillation. A low-molecular-weight heparin was chosen for long-term treatment. CONCLUSION: A low-molecular-weight heparin appears to be the most appropriate way to maintain effective and safe anticoagulation in this patient. Coumarins carry a residual risk of an extrahepatic, immunologically mediated cross-sensitization. Long-term use of ximelagatran may also cause liver damage. For heparinoids, hirudins, and other drugs affecting coagulation like platelet aggregation inhibitors, therapeutic evidence is not sufficient. Though subcutaneous application of heparin is a disadvantage for the patient, therapeutic alternatives do not have better documented efficacy or less hepatotoxic potential. The low-molecular-weight heparin fulfills the criteria for refunding set by federal jurisdiction.

Anticoagulants↗