Warfarin oral bioavailability

Uncertain, but it is suggested that the St John s wort increases the metabolism and clearance of the anticoagulants possibly by induction of cytochrome P450 isoenzymes. It affected both R- and 5-warfarin. Oral bioavailability was not altered. ... 

Sitaxsentan is a potent and selective agent which inhibits ET-1 binding to ETA receptors (IC50 = 1.4 nM), while being essentially inactive at ETB receptors (IC50 = 9.8 pM).23 In the clinic, it was found to have excellent oral bioavailability (70-100%) and a terminal elimination half-life of 10 h, and is administered as a once daily 100 mg dose. It is highly protein bound in plasma (> 99%) and extensively metabolized in the liver to inactive metabolites, predominantly by CYPs 2C9 and 3A4. Excretion is 50 60% renal, with the balance in the feces.25 Sitaxsentan inhibits CYP 2C9, and was observed to increase exposure to warfarin by over twofold. The use of cyclosporine A is also contraindicated, but no interactions were observed with sildenafil.15 Sitaxsentan was well tolerated in trials, with only minor side effects reported. Reversible liver enzyme abnormalities were also observed, but less frequently than with bosentan.15 25... 

Studies have shown that gastrointestinal mucus presents a physical barrier to the diffusion of small molecules such as urea, benzoic acid, antipyrine, 1-phenylalanine and warfarin as well as to large protein molecules. Similarly, the passive absorption of testosterone was shown to be doubled upon ridding the intestinal epithelial cells of the overlying mucus layer. However, the situation regarding the effect of mucus on oral bioavailability is a complex one for example, it has been shown that drag binding to the mucosal surface is essential to the absorption of barbituric acid derivatives from the rat small intestine. 

Drug-drug interactions A 71-year-old woman taking 400 mg per day miconazole oral gel four times daily was admitted to hospital because of massive proteinuria (10 g per day) and systemic oedema [20 ]. She received oral prednisolone, cyclosporine (150 mg per day) and was also treated with warfarin (2-2.5 mg per day). Increased oral bioavailability of warfarin and cyclosporine were suggested her INR had increased to 7.25 and cyclosporine trough concentration had increased from 132.9 to 1296.5 ng/ml. Also, a significant miconazole plasma concentration (0.35 ng/ml) was measured. Miconazole was discontinued, amphotericin B was started and cyclosporine A dose was adjusted to 125 mg per day. 

Vitamins Ki and K2 require bile salts for absorption from the intestinal tract. Vitamin Kl is available clinically in oral and parenteral forms. Onset of effect is delayed for 6 hours but the effect is complete by 24 hours when treating depression of prothrombin activity by excess warfarin or vitamin deficiency. Intravenous administration of vitamin Ki should be slow, because rapid infusion can produce dyspnea, chest and back pain, and even death. Vitamin repletion is best achieved with intravenous or oral administration, because its bioavailability after subcutaneous administration is erratic. Vitamin Ki is... 

May cause mild CNS and GI effects and 1 bioavailability of drugs that require acidity for oral absorption (e.g., fluoroquinolones, ketoconazole). Inhibit P450 — >L elimination of diazepam, phenytoin, and warfarin. 

The bioavailability of warfarin is nearly complete when the drug is administered orally, intravenously, or rectally. Different commercial preparations of warfarin tablets vary in their rate of dissolution, and this causes some variation in the rate and extent of absorption. Food in the GI tract also can decrease the rate of absorption. Warfarin usually is detectable in plasma within 1 hour of its oral administration, and concentrations peak in 2-8 hours. 

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