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Author Hallak, H. O. ♦ Wedlund, P. J. ♦ Modi, M. W. ♦ Lewis, G. L. ♦ Woodruff, B. ♦ Trowbridge, A. A. ♦ Patel, I. H.
Source PubMed Central
Content type Text
File Format PDF
Language English
Difficulty Level Medium
Subject Domain (in DDC) Technology ♦ Medicine & health
Abstract A 30 year old black male required a 60 mg daily dose of warfarin to elicit a therapeutic anticoagulant response (normal warfarin dose 2.5-10 mg day-1; maximum 15 mg day-1). Hereditary warfarin resistance was suspected after compliance, diet, concurrent medication and any gastrointestinal disorder were eliminated as contributory causes. The disposition of vitamin K and vitamin K epoxide was examined in the propositus, his two sisters and 13 control black male subjects. Each subject was given an i.v. bolus dose (5 mg) of vitamin K prior to and after 2 weeks of warfarin therapy (5 mg day-1). The oral clearances of (S)- and (R)-warfarin were also measured in each subject during the last day of warfarin therapy. The mean (+/- s.d.) systemic clearance of vitamin K was similar in all subjects before (114 +/- 35 ml min-1) and after (112 +/- 40 ml min-1) warfarin therapy. The mean (+/- s.d.) AUC value for vitamin K epoxide was increased by warfarin treatment (6.5 +/- 5.4 micrograms ml-1 min before and 139 +/- 78 micrograms ml-1 min after) in all subjects. In the propositus, the oral clearance of (S)-warfarin (14.5 ml min-1) and the clearance ratio for (S)/(R)warfarin (2.6) differed by more than 7 standard deviations from the control group (4.3 +/- 1.1 ml min-1 and 1.2 +/- 0.2, respectively). In one sister of the propositus, the stereoselective disposition of warfarin was comparable with that of her brother ((S)-warfarin clearance = 16.2 ml min-1; and (S)/(R)-warfarin clearance ratio = 2.7).
ISSN 13652125
Age Range above 22 year
Educational Use Research
Interactivity Type Expositive
Education Level UG and PG
Learning Resource Type Article
Publisher Date 1993-03-01
e-ISSN 13652125
Journal British Journal of Clinical Pharmacology
Volume Number 35
Issue Number 3
Starting Page 327


Source: PubMed Central