Warfarin dosing and the promise of pharmacogenomics.

Due to its narrow therapeutic index and substantial inter-patient variability in clinical response, warfarin represents an ideal drug candidate to benefit from the promise of pharmacogenomic-guided dosing strategies. Consistent with in vitro data, clinical studies have demonstrated that CYP2C9 polymorphisms significantly influence warfarin pharmacokinetics by reducing (S)-warfarin metabolic clearance, consequently lowering maintenance dose requirements and increasing the risk over-anticoagulation during the initiation phase of therapy. Recent data suggest that polymorphisms in genes encoding several pharmacodynamic determinants of the coagulation cascade may also influence warfarin's antithrombotic dose-response.

Pharmacokinetics and metabolic profile of free, conjugated, and total silymarin flavonolignans in human plasma after oral administration of milk thistle extract.

Silymarin, a mixture of polyphenolic flavonoids extracted from milk thistle (Silybum marianum), is composed mainly of silychristin, silydianin, silybin A, silybin B (SB(B)), isosilybin A (ISB(A)), and isosilybin B. In this study, the plasma concentrations of free (unconjugated), conjugated (sulfated and glucuronidated), and total (free and conjugated) silymarin flavonolignans were measured using liquid chromatography-electrospray ionization-mass spectrometry, after a single oral dose of 600 mg of standardized milk thistle extracts to three healthy volunteers. Pharmacokinetic analysis indicated that silymarin flavonolignans were rapidly eliminated with short half-lives (1-3 and 3-8 h for free and conjugated, respectively).