Disease relevance of Falithrom

• Coronary events (coronary death and nonfatal recurrent myocardial infarctions) were lower in the ASA group (24 events) than in the placebo (37 events) (p less than 0.07) or phenprocoumon group (32 events) [1].
• There were 13 coronary deaths (fatal myocardial infarction and sudden death) in the ASA group, 22 in the placebo group and 26 in the phenprocoumon group [1].
• In the present study, we evaluated the effect of phenprocoumon on shunt patency after TIPSS placement using Palmaz stents; 49 patients with Child's A and B cirrhosis, who underwent successful TIPSS placement were randomized into the treatment group (n = 24) who received phenprocoumon and a control group (n = 25) [2].
• Phenprocoumon-induced hepatitis delaying precise diagnosis in a thrombophilic patient with activated protein C resistance due to factor V R506Q mutation [3].
• 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].

Psychiatry related information on Falithrom

• After 130 patients had electively received a femoropopliteal vein graft, they were randomly assigned to a therapy group (treatment with phenprocoumon [n = 66]) or to a control group (n = 64) that remained without any anticoagulant treatment [5].

High impact information on Falithrom

• During the screening of thrombophilic patients we identified a patient, who was using marcoumar, with 0% PS by monoclonal ELISA and 23% PS by polyclonal ELISA [6].
• Phenylbutazone markedly increased both the phenprocoumon concentrations and prothrombin times, whereas sulfinpyrazone did not [7].
• In conclusion, the VKORC1 genotype modifies the effect of the CYP2C9 genotype on phenprocoumon dose requirements [8].
• We used linear regression models and Cox proportional hazard models to determine the effects of the VKORC1 and CYP2C9 genotypes on phenprocoumon dose requirements, overanticoagulation, and time to achieve stability [8].
• OBJECTIVE: Our objective was to assess whether there is an association between the presence of allelic variants of the gene for cytochrome P450 (CYP) 2C9 and anticoagulation problems during the initial phase of phenprocoumon treatment [9].

Chemical compound and disease context of Falithrom

• 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 [10].
• Consecutive patients with atrial fibrillation and/or prosthetic heart valves, receiving chronic anticoagulation with phenprocoumon and scheduled to undergo cardiac catheterization, were randomized to subcutaneous enoxaparin twice daily (n = 32) or intravenous UFH (n = 36) [11].
• However, there were only two coumarin embryopathies (0.6%; both phenprocoumon) [12].
• Secondary prevention of myocardial infarction. Comparison of acetylsalicylic acid, phenprocoumon and placebo. A multicenter two-year prospective study [13].
• Disappearance of migraine during the use of warfarin and of phenprocoumon has been described in sporadic case reports [14].

Biological context of Falithrom

• Daily blood samples were drawn for phenprocoumon content and one-stage prothrombin time [7].
• 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 [15].
• VKORC1 and CYP2C9 Genotypes and Phenprocoumon Anticoagulation Status: Interaction Between both Genotypes Affects Dose Requirement [8].
• The protein binding of racemic phenprocoumon was between that of the enantiomers [16].
• Drug interactions as a cause of overanticoagulation on phenprocoumon or acenocoumarol predominantly concern antibacterial drugs [17].

Anatomical context of Falithrom

• Stereochemical aspects of the metabolism of phenprocoumon in rat liver microsomes [18].
• Phenprocoumon was essentially irreversibly bound to the microsomes [19].
• Samples of urine and feces were collected daily from a normal human volunteer who had received a dose of pseudoracemic phenprocoumon [an equimolar mixture of (R)-[12C]- and (S)-[2-13C]phenprocoumon] containing a tracer dose of 10 microCi of [14C]phenprocoumon and analyzed by TLC, HPLC, and GC-MS [20].
• Here we present the case of a 56-year-old woman who developed recurrent episodes of severe hepatitis following repeated exposure to phenprocoumon (Marcumar; Roche, Grenzach-Wyhlen, Germany) and warfarin (Coumadin; DuPont Pharma, Bad Homburg, Germany) after replacement of the mitral valve with a mechanical prosthesis [21].
• Endoscopic finding of an intramural haemorrhage in the duodenum under anticoagulant therapy with phenprocoumon [22].

Associations of Falithrom with other chemical compounds

• The pharmacodynamics and pharmacokinetics of the optical enantiomers of phenprocoumon were studied in 5 normal subjects and compared to the racemic mixture [16].
• The most important of these is CYP2C9, which hydroxylates the S-enantiomers of warfarin, acenocoumarol and phenprocoumon with high catalytic activity [23].
• Five patients with phenprocoumon-induced hepatitis recovered well after anticoagulation was switched to another coumarin derivate or subcutaneous low molecular weight heparin [24].
• In a multi-centre (n = 12), observational, prospective study we compared 666 pregnant women exposed to phenprocoumon (n = 280), acenocoumarol (n = 226), fluindione (n = 99), warfarin (n = 63) and phenindione (n = 2) to a non-exposed control group (n = 1,094) [12].
• In this paper we present the following observations: 1) In sheep vitamin K-antagonists like phenprocoumon induce a decrease of the serum levels of osteocalcin (bone Gla-protein) and of the affinity of the circulating osteocalcin for hydroxyapatite [25].

Gene context of Falithrom

• Identification of cytochromes P450 2C9 and 3A4 as the major catalysts of phenprocoumon hydroxylation in vitro [26].
• ORM 1 and human native AGP preferred the binding of (S)-enantiomers of warfarin and acenocoumarol, while no enantioselectivity was observed in phenprocoumon binding [27].
• The less important role of CYP2C9 for the clearance of phenprocoumon is due to the involvement of CYP3A4 as an additional catalyst of phenprocoumon hydroxylation and significant excretion of unchanged drug in bile and urine, while the elimination of warfarin and acenocoumarol is almost completely by metabolism [28].
• Since the synthesis of PC depends on the availability of vitamin K, patients receiving phenprocoumon have also been analyzed [29].
• In the course of a human volunteer study investigating the influence of CYP (cytochrome) 2C9 genetic polymorphism on phenprocoumon (PPC) metabolism, we used this new two-dimensional online analytical technique for the analysis of PPC metabolites in plasma [30].

Analytical, diagnostic and therapeutic context of Falithrom

• Phenprocoumon for prevention of shunt occlusion after transjugular intrahepatic portosystemic stent shunt: a randomized trial [2].
• In patients with preserved liver function occlusion of the shunt may be prevented by phenprocoumon treatment in the first 3 months after TIPSS placement [2].
• Weekly management with phenprocoumon led to a 6.5% improvement (95% CI, 0.0%-13.1%) in time in the international normalized ratio target range when patients were managed at an anticoagulation clinic and to an 8.7% improvement (95% CI, 1.6%-15.9%) when patients were self-managed [31].
• Weekly management of OAT with long-acting phenprocoumon has to be preferred at anticoagulation clinics or, where possible, through patient self-management [31].
• METHODS: We conducted a population-based cohort study among patients of an anticoagulation clinic who were treated with acenocoumarol or phenprocoumon between April 1, 1991, and May 31, 2003, and whose CYP2C9 status was known [32].

References