Influence of age, performance status, body weight, and tumor type in individuals with cancer on the disposition of warfarin and its enantiomers: Department of Veterans Affairs cooperative study number 75.
Plasma warfarin and its R,S enantiomer concentrations, one-stage prothrombin times, and mean daily warfarin doses were analyzed in 196 patients given warfarin. These individuals were part of a controlled clinical trial that examined the effect of warfarin as an adjuvant to "standard" treatment in a variety of malignancies. Neither the plasma warfarin concentration nor the daily warfarin dose required to produce a given degree of prothrombin-time prolongation was influenced by age or body weight in these subjects. When the data were analyzed by performance status, we noted several variations of interest. Individuals with different tumor types demonstrated disparities in warfarin disposition. Patients with colorectal cancer, for example, required lower mean daily warfarin doses to achieve a given degree of one-stage prothrombin time prolongation. Analysis of warfarin enantiomers (R,S) in a selected group of patients demonstrated a lower-than-normal ratio (2:1) for the colorectal cancer group (1.42:1) because of an apparent decrease in the plasma R component. In contrast, patients with head and neck cancer demonstrated a ratio of 2.85:1, and the R component was elevated. Warfarin disposition and the effect of warfarin on vitamin K-dependent clotting factor production were altered in the patients with cancer reported in this study. The mechanisms for these alterations are complex and not completely understood.
Forman
W B
WB
University of New Mexico Cancer Center, Albuquerque 87131.
Cook
C E
CE
Zacharski
L R
LR
Moritz
T E
TE
Henderson
W G
WG
Hoppel
C
C
Rickles
F R
FR
D000375:Aging / Q000502:physiology*; D001835:Body Weight / Q000502:physiology*; D015179:Colorectal Neoplasms / Q000097:blood / Q000188:drug therapy / Q000473:pathology; D006258:Head and Neck Neoplasms / Q000097:blood / Q000188:drug therapy / Q000473:pathology; D006801:Humans; D009369:Neoplasms / Q000097:blood* / Q000188:drug therapy / Q000473:pathology; D011446:Prospective Studies; D011517:Prothrombin Time; D011597:Psychomotor Performance / Q000502:physiology*; D013237:Stereoisomerism; D014481:United States; D014493:United States Department of Veterans Affairs; D014859:Warfarin / Q000097:blood* / Q000627:therapeutic use
D014859:Warfarin