Influence of acute viral hepatitis on disposition and pharmacologic effect of warfarin

Williams, Roger L.; Schary, William; Blaschke, Terrence F.; Meffin, Peter J.; Melmon, Kenneth L.; Rowland, Malcolm

doi:10.1002/cpt197620190

Cited by 38 publications

(8 citation statements)

References 7 publications

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“…These results are consistent with a previous report that the disposition of warfarin is not affected by mild or moderate hepatic impairment (23). However, since maximal levels of AST and ALT were within 5 times of the upper range, a cautious approach is needed when applying our results to the patients who have severe liver function abnormalities.…”

Section: Discussionsupporting

confidence: 94%

Risk Factors of Drug Interaction between Warfarin and Nonsteroidal Anti-Inflammatory Drugs in Practical Setting

et al. 2010

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Nonsteroidal anti-inflammatory drugs (NSAIDs) are known to interact with the oral anticoagulant warfarin and can cause a serious bleeding complication. In this study, we evaluated the risk factors for international normalized ratio (INR) increase, which is a surrogate marker of bleeding, after addition of an NSAID in a total of 98 patients who used warfarin. Patient age, sex, body mass index, maintenance warfarin dose, baseline INR, coadministered medications, underlying diseases, and liver and kidney functions were evaluated for possible risk factors with INR increase ≥15.0% as the primary end-point. Of the 98 patients, 39 (39.8%) showed an INR elevation of ≥15.0% after adding a NSAID to warfarin therapy. Multivariate analysis showed that high maintenance dose (>40 mg/week) of warfarin (P=0.001), the presence of coadministered medications (P=0.024), the use of meloxicam (P=0.025) and low baseline INR value (P=0.03) were the risk factors for INR increase in respect to NSAID-warfarin interaction. In conclusion, special caution is required when an NSAID is administered to warfarin users if patients are taking warfarin >40 mg/week and other medications interacting with warfarin.

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Section: Discussionsupporting

confidence: 94%

Risk Factors of Drug Interaction between Warfarin and Nonsteroidal Anti-Inflammatory Drugs in Practical Setting

et al. 2010

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“…2 The values for Vd reported here (0.12 to 0.25 L/kg) are in accord with the ap-parent volume of distribution reported by others!' 2, 25, 28 as are the clearance values.1, 2,25,27,28 While nonsmoking steady-state warfarin plasma levels were slightly though consistently higher than smoking phase levels, there was no detectable increase in the steady-state prothrombin time ratios. This may be explained by the barely perceptible pharmacologic effect of warfarin at steady-state plasma levels established!5 and the lack of sensitivity and inherent variability of prothrombin time determinations.…”

Section: Discussionmentioning

confidence: 98%

Smoking and warfarin disposition

Bachmann

Shapiro

Fulton

et al. 1979

Clin Pharma and Therapeutics

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Nine cigarette smokers ingested an average daily 0.032 mg/kg dose of sodium warfarin for 2 wk while continuing to smoke and for an additional 2 wk after having abstained from cigarette smoking for a month washout phase. Steady-state plasma levels of warfarin, clearances, t 1/2, apparent volumes of distribution, steady-state prothrombin times, and plasma thiocyanate levels were measured during both the smoking and nonsmoking phases. During the nonsmoking phase there was a 13% increase in average steady-state warfarin level and a 13% decrease in warfarin clearance rate. There also was a 23% increase in warfarin t 1/2 and an 11% increase in the apparent volume of distribution. Prothrombin time did not change. Thiocyanate levels were 3 to 4 times as high during the smoking than the nonsmoking phase. It appears that cigarette smoking does affect warfarin clearance, t 1/2, and apparent volume of distribution, though the net effect on warfarin's pharmacodynamic activity is negligible, at least at doses which are ineffective therapeutically.

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“…Warfarin clearance and protein binding are unaltered in patients with acute viral hepatitis during or after the acute episode (Williams et al 1976), but increased sensitivity to anticoagulant therapy, probably secondary to impaired protein synthesis, occurs in viral hepatitis as indicated by histological abnormalities of rough endoplasmic reticulum in the hepatocytes (Schaffner 1970).…”

Section: Plasma Warfarinmentioning

confidence: 99%

Clinical Pharmacokinetic Considerations in the Control of Oral Anticoagulant Therapy

Shetty

Fennerty

Routledge

1989

Clinical Pharmacokinetics

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Aspects of the pharmacokinetics of warfarin that are clinically relevant are reviewed here. Since warfarin is normally completely absorbed, resistance to treatment due to impaired absorption is unusual, even in severe short bowel syndrome. Warfarin is highly albumin-bound; thus, hypoalbuminaemic states result in an increased free fraction of the drug and a decreased half-life but, as might be expected, there is no evidence of altered response at steady-state. Warfarin is completely metabolised by the liver to hydroxy-warfarins and warfarin alcohols, and although the latter have some biological activity they do not contribute significantly to the drug effect. No information is available concerning the metabolism of warfarin in chronic liver disease, but there is evidence of increased sensitivity due to impaired vitamin K-dependent clotting factor synthesis. Impaired renal function does not appear to alter the effect of warfarin. Lowered response to the drug may be secondary to poor compliance, kinetic resistance or pharmacodynamic resistance. These factors can be identified using algorithms based on population values for plasma warfarin concentrations and clearances at steady-state. The pharmacokinetics and pharmacodynamics of warfarin indicate that several days' overlap with heparin on initiation of warfarin, and gradual (rather than sudden) discontinuation of warfarin, might theoretically be necessary. However, those studies which have been performed have indicated that a long overlap and gradual discontinuation are not associated with greater safety or efficacy of the drug. Because of the long elimination half-life of warfarin and the short elimination half-life of vitamin K, many days' treatment with phytomenadione may be required after warfarin overdose. The elimination half-life and therefore the duration of therapy may be reduced by regular oral cholestyramine, although the means by which the latter enhances warfarin elimination is still unknown.

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Influence of acute viral hepatitis on disposition and pharmacologic effect of warfarin

Cited by 38 publications

References 7 publications

Risk Factors of Drug Interaction between Warfarin and Nonsteroidal Anti-Inflammatory Drugs in Practical Setting

Risk Factors of Drug Interaction between Warfarin and Nonsteroidal Anti-Inflammatory Drugs in Practical Setting

Smoking and warfarin disposition

Clinical Pharmacokinetic Considerations in the Control of Oral Anticoagulant Therapy

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