Warfarin plasma levels

MacDonald MG, Robinson DS, Sylwester D, Jaffe JJ. The effects of phenobarbital, chloral betaine, and glntethimide administration on warfarin plasma levels and hypopro-thrombinemic responese in man. Chn Pharmacol Ther 1969 10(l) 80-4. 

In a study, warfarin plasma levels were increased by 65% by flu-voxamine, and raised INRs have been seen in several cases. In another study with warfarin and paroxetine, the majority of patients experienced no interaction, but a few had minor bieeding events. Other studies suggest that citaiopram and sertraiine do not signiilcantiy aiter the pharmacokinetics or effects of warfarin. However, isoiated reports describe bieeding in patients taking SSRIs and coumarins or fluindione, and SSRIs aione have, rareiy, been associated with bieeding. 

Increased INR was observed in healthy volunteers orally administered 1000 mg cranberry juice concentrate (equivalent to 57 g of cranberries) daily, before or after single doses of 25 mg warfarin. Plasma levels of warfarin were unchanged (Abdul et al. 2008). 

Administration of zafirlukast and aspirin increases plasma levels of zafirlukast, When zafirlukast is administered with warfarin, there is an increased effect of the anti coagulant. Administration of zafirlukast and theophylline or erythromycin may result in a decreased level of zafirlukast. Administration of montelukast with other drugs has not revealed any adverse responses. Administration of montelukast with aspirin and NSAIDs is avoided in patients with known aspirin sensitivity. Administration of zileuton with propranolol increases the activity or the propranolol with theophylline increases serum theophylline levels and with warfarin may increase prothrombin time (PT). A prothrombin blood test should be done regularly in the event dosages of warfarin need to be decreased. 

Orlistat reduces the absorption of fat-soluble vitamins. Daily intake of a multivitamin containing vitamins A, D, E, and K, as well as 3-carotene, is recommended. Patients should take the multivitamin 2 hours prior to or after the dose of orlistat.31 Since availability of vitamin K may decline in patients receiving orlistat therapy, close monitoring of coagulation status should occur with concomitant administration of warfarin.31 Administration of orlistat in conjunction with cyclosporine can result in decreased cyclosporine plasma levels. To avoid this interaction, cyclosporine should be taken 2 hours preceding or following the dose of orlistat. Additionally, cyclosporine levels should be monitored more frequently.31... 

Drugs that are not absorbed from the gastrointestinal tract of the baby, such as warfarin, are safe for the mother to take. The administration of antibiotics to a breast-feeding mother usually poses no concern for the newborn infant. However, metronidazole, which has mutagenic properties, reaches concentrations in milk that equal or exceed maternal plasma levels. Caution is also advised with sulphonamides, nitrofurantoin, or naladixic acid since these can cause haemolysis in infants with glucose-6-phosphate dehydrogenase deficiency. 

Many drugs are bound to circulating albumin. Hypoalbuminemia also increases plasma levels of free drugs, which may be counterbalanced by faster metabolism. Increased levels of the free drug may be clinically relevant as demonstrated for prednisolone (B6) and possibly warfarin. 

Warfarin is rapidly and nearly completely absorbed by the oral route. Peak plasma levels typically occur within 2-8 h. Warfarin is highly protein bound 97-99%. The volume of distribution approximates 0.151 kg Warfarin is extensively metabolized by hepatic microsomal enzymes. The primary metabolites are 6- and 7-hydroxy warfarin via oxidation and several warfarin alcohols via reduction. The warfarin alcohols retain weak anticoagulant activity. The metabolites undergo enterohepatic circulation. Approximately 85 % of warfarin appears in the urine as metabolites. Less than 1% or 2% appears in the urine unchanged. Warfarin metabolites are also excreted in the stool. The plasma half-life varies widely, from 10 to 80 h it is typically 36-44 h. The duration of clinical effects can significantly exceed the half-life of warfarin. (Note There are many drug interactions with warfarin the reader is referred to a standard pharmacology text for further details.)... 

Warfarin is heavily plasma protein-bound (> 97 percent). It therefore interacts with other protein-bound drugs (e.g., carbamazepine, phenytoin, and benzodiazepines) in that binding of warfarin to plasma proteins may displace bound drug that is administered as concurrent therapy. Thus, toxicity may result, due to elevated plasma levels, and the clearance rate of the drug may increase to compensate. 

Concentrated solutions of quinine may cause abscesses when injected intramuscularly or thrombophlebitis when infused intravenously. GI absorption of quinine can be delayed by antacids containing aluminum. Quinine and quinidine can elevate plasma levels of digoxin. Likewise, the alkaloid may raise plasma levels of warfarin. The action of quinine at neuromuscular junctions will enhance the effect of neuromuscular blocking agents and oppose the action of acetylcholinesterase inhibitors. Prochlorperazine can amplify quinine s cardiotoxicity, as can halo-fantrine. The clearance of quinine is decreased by cimetidine and increased by acidification of the urine and by rifampin. 

Which one of the following drugs is most likely to increase plasma levels of alprazolam, theophylline, and warfarin... 

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