Linked Life Data

11452703

Source:http://linkedlifedata.com/resource/pubmed/id/11452703

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
7
pubmed:dateCreated
2001-7-16
pubmed:abstractText
Evidence for the selectivity of S-warfarin metabolism by CYP2C9 is substantial, suggesting that warfarin may be a potential CYP2C9 phenotyping probe. It is, however, limited by its ability to elevate the international normalized ratio (INR) and potentially cause bleeding. The effect of vitamin K to attenuate the elevation of INR may enable the safe use of warfarin as a probe. The objective of this study was to investigate the pharmacokinetics and pharmacodynamics of S- and R-warfarin in plasma following the administration of warfarin alone versus warfarin and vitamin K in CYP2C9*1 homozygotes. Healthy adults received, in a randomized crossover fashion in a fasted state, warfarin 10 mg orally or warfarin 10 mg plus vitamin K 10 mg orally. Blood samples were obtained over 5 days during each phase. INR measurements were obtained at baseline and day 2 in each phase. INR, AUC0-infinity, and t1/2 of plasma S- and R-warfarin were examined. Eleven CYP2C9*1 homozygotes (3 men, 8 women) were enrolled. INR at day 2 following warfarin 10 mg was 1.18 +/- 0.19, which differed significantly from baseline (INR = 1.00 +/- 0.05) and warfarin with vitamin K (INR = 1.06 +/- 0.07). INR at baseline was not significantly different from warfarin with vitamin K. t1/2 and AUC0-infinity of both enantiomers did not significantly differ between the phases. It was concluded that INR is apparently attenuated by concomitant administration of a single dose of vitamin K without affecting the pharmacokinetics of either warfarin stereoisomer. Warfarin 10 mg may be safely used as a CYP2C9 probe in *1 homozygotes when given concomitantly with 10 mg of oral vitamin K.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
0091-2700
pubmed:author
pubmed:issnType
Print
pubmed:volume
41
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
715-22
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed-meshheading:11452703-Administration, Oral, pubmed-meshheading:11452703-Adult, pubmed-meshheading:11452703-Anticoagulants, pubmed-meshheading:11452703-Antifibrinolytic Agents, pubmed-meshheading:11452703-Area Under Curve, pubmed-meshheading:11452703-Aryl Hydrocarbon Hydroxylases, pubmed-meshheading:11452703-Chromatography, High Pressure Liquid, pubmed-meshheading:11452703-Cross-Over Studies, pubmed-meshheading:11452703-Cytochrome P-450 Enzyme System, pubmed-meshheading:11452703-Female, pubmed-meshheading:11452703-Genotype, pubmed-meshheading:11452703-Half-Life, pubmed-meshheading:11452703-Humans, pubmed-meshheading:11452703-International Normalized Ratio, pubmed-meshheading:11452703-Male, pubmed-meshheading:11452703-Stereoisomerism, pubmed-meshheading:11452703-Steroid 16-alpha-Hydroxylase, pubmed-meshheading:11452703-Steroid Hydroxylases, pubmed-meshheading:11452703-Vitamin K, pubmed-meshheading:11452703-Warfarin
pubmed:year
2001
pubmed:articleTitle
Effects of oral vitamin K on S- and R-warfarin pharmacokinetics and pharmacodynamics: enhanced safety of warfarin as a CYP2C9 probe.
pubmed:affiliation
Clinical Pharmacology Research Center, Bassett Healthcare, Cooperstown, New York, USA.
pubmed:publicationType
Journal Article, Clinical Trial, Research Support, U.S. Gov't, P.H.S., Randomized Controlled Trial