Ethoxy-, pentoxy- and benzyloxyphenoxazones and homologues: a series of substrates to distinguish between different induced cytochromes P-450.

Relationship between nutritional status and the glomerular filtration rate: Results from the MDRD Study

Differential effects of phenobarbitone and 3-methylcholanthrene induction on the hepatic microsomal metabolism and cytochrome P-450-binding of phenoxazone and a homologous series of its n-alkyl ethers (alkoxyresorufins).

Vitamin K antagonists belong to the group of most frequently used drugs worldwide. They are used for long-term anticoagulation therapy, and exhibit their anticoagulant effect by inhibition of vitamin K epoxide reductase. Each drug exists in two different enantiomeric forms and is administered orally as a racemate. The use of vitamin K antagonists is complicated by a narrow therapeutic index and an unpredictable dose-response relationship, giving rise to frequent bleeding complications or insufficient anticoagulation. These large dose response variations are markedly influenced by pharmacokinetic aspects that are determined by genetic, environmental and possibly other yet unknown factors. Previous knowledge in this regard principally referred to warfarin. Cytochrome P450 (CYP) 2C9 has clearly been established as the predominant catalyst responsible for the metabolism of its more potent S-enantiomer. More recently, CYP2C9 has also been reported to catalyse the hydroxylation of phenprocoumon and acenocoumarol. However, the relative importance of CYP2C9 for the clearance of each anticoagulant substantially differs. Overall, the CYP2C9 isoenzyme appears to be most important for the clearance of warfarin, followed by acenocoumarol and, lastly, phenprocoumon. 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. Consequently, the effects of CYP2C9 polymorphisms on the pharmacokinetics and anticoagulant response are also least pronounced in the case of phenprocoumon; this drug seems preferable for therapeutic anticoagulation in poor metabolisers of CYP2C9. In addition to these vitamin K antagonists, oral thrombin inhibitors are currently under clinical development for the prevention and treatment of thromboembolism. Of these, ximelagatran has recently gained marketing authorisation in Europe. These novel drugs all feature some major advantages over traditional anticoagulants, including a wide therapeutic interval, the lack of anticoagulant effect monitoring and a low drug-drug interaction potential. However, they are also characterised by some pitfalls. Amendments of traditional anticoagulant therapy, including self-monitoring of international normalised ratio values or prospective genotyping for individual dose-tailoring may contribute to the continuous use of warfarin, phenprocoumon and acenocoumarol in the future.

Comparative pharmacokinetics of vitamin K antagonists: warfarin, phenprocoumon and acenocoumarol.

https://www.kidney-international.org/article/S0085-2538(15)60235-6/pdf

Effect of dietary protein restriction on nutritional status in the Modification of Diet in Renal Disease Study

4-Hydroxycoumarin/2-hydroxychromone tautomerism: Infrared spectra of 2-13c and 3-D labeled 4-hydroxycoumarin and its anion

https://www.ajkd.org/article/S0272-6386(83)80067-5/pdf

Adsorption of insulin to the surface of peritoneal dialysis solution containers.

Changes in the metabolic profiles of R- and S-warfarin and R- and S-phenprocoumon as a probe to categorize the effect of inducing agents on microsomal hydroxylases.

William R. Porter

Papers

4-Hydroxycoumarin/2-hydroxychromone tautomerism: Infrared spectra of 2-13c and 3-D labeled 4-hydroxycoumarin and its anion

Adsorption of insulin to the surface of peritoneal dialysis solution containers.

Changes in the metabolic profiles of R- and S-warfarin and R- and S-phenprocoumon as a probe to categorize the effect of inducing agents on microsomal hydroxylases.

4‐Hydroxycoumarin/2‐hydroxychromone tautomerism: Infrared spectra of 3‐substituted‐2‐13c‐4‐hydroxycoumarins

New method for the resolution of racemic warfarin and its analogues using low-pressure liquid chromatography.