A subtherapeutic international normalized ratio despite increasing doses of warfarin: could this be malabsorption?
OBJECTIVE
To describe a case of warfarin resistance apparently caused by malabsorption and to review the literature regarding warfarin resistance.


METHODS
A 28-year-old renal transplant patient with systemic lupus erythematosus was admitted for upper extremity thrombophlebitis. Resistance to oral warfarin was demonstrated. Potential causes were investigated. The trapezoidal rule was used to compare the area under the curve for intravenous versus oral dosing of warfarin. The usual bioavailability of warfarin should be 100%. In this patient, warfarin bioavailability after oral dosing was 1.5%. Three potential causes, malabsorption (FF), enzymatic degradation (FG), and first-pass extraction in the portal circulation (FH), are discussed.


CONCLUSIONS
This case demonstrates resistance to warfarin presumably caused by malabsorption.
Lara
L F
LF
Department of Internal Medicine, Northeastern Ohio Universities College of Medicine, Affiliated Hospitals at Canton, USA.
Delgado
L L
LL
Frazee
L A
LA
Haupt
K M
KM
Rutecki
G W
GW
D000284:Administration, Oral; D000328:Adult; D000925:Anticoagulants / Q000008:administration & dosage / Q000378:metabolism / Q000493:pharmacokinetics / Q000627:therapeutic use; D019540:Area Under Curve; D001682:Biological Availability; D004305:Dose-Response Relationship, Drug; D004351:Drug Resistance; D005260:Female; D006801:Humans; D007275:Injections, Intravenous; D007408:Intestinal Absorption / Q000502:physiology*; D016030:Kidney Transplantation; D014859:Warfarin / Q000008:administration & dosage* / Q000378:metabolism* / Q000493:pharmacokinetics / Q000627:therapeutic use
D000925:Anticoagulants; D014859:Warfarin