Warfarin is a combination of R- as well as S-enantiomers. The human S-enantiomer is more active than the R-enantiomer (2-5 times), but the half-life of the latter is longer.
After ingestion, the substance is almost completely absorbed from the digestive tract, reaching a peak in the first 4 hours.
There are no significant differences in the values of the distribution volume for intravenous injection and ingestion. The distribution level is rather low - about 0.14 l / kg. The distribution stage is 6-12 hours. The substance can penetrate the placental barrier, reaching indicators that are close to the level of concentration in the mother, but it is not observed inside the mother's milk. About 99% of the drug is synthesized with a plasma protein.
The excretion of the substance takes place in the form of inactive decay products. The drug is stereoselectively metabolized using microsomal hepatic enzymes (hemoprotein type P-450), turning into inactive hydroxylated degradation products (mainly), and also reductase (this method forms warfarin alcohols). The latter have a weak anticoagulant effect.
The decay products of the active ingredient are excreted primarily through the kidneys, and a small part of them with bile. Discovered decay products of the substance: dehydrarfarine with two diastereoisomers of alcohol, and in addition 4'-, 6- and 7-, and also 8- and 10-hydroxyarfarin. Participants in the exchange processes are the following isoenzymes: 2C9 and 2C19 with 2C8, and in addition 2C18 with 1A2 and 3A4. Isoenzyme 2C9, most likely, should be considered the leading type of hemoprotein P-450 within the human liver, responsible for the anticoagulant effect of the substance in the form in vivo.
The terminal half-life of warfarin for one-time use is about the 1st week, but the real half-life is between 20-60 hours (the average is 40 hours). The R-warfarin clearance rate is half that of S-warfarin, but because their distribution volumes are similar, the half-life of the R-enantiomer is longer than that of the S-enantiomer. The half-life of the R-enantiomer is about 37-89 hours, and for the S-enantiomer, within 21-43 hours.
Tests using radioactively labeled warfarin demonstrated that in the urine, more than 92% of the ingested drug is observed. Only a small part of the substance is excreted unchanged; excretion is mainly carried out in the form of decay products.