The influence of age, liver size and enantiomer concentrations on warfarin requirements.
1. We have tested the hypothesis that the fall in hepatic mass with age influences the age related increase in sensitivity to warfarin. In 39 otherwise healthy outpatients, aged 50-87 years, stabilised on warfarin for prophylaxis of thromboembolism, age, mean International Normalised Ratio (INR), and mean warfarin dosage were recorded. Liver volume was measured by ultrasound, and plasma was assayed for trough concentrations of (R)- and (S)-warfarin. 2. There was a negative correlation between age and liver volume (r = -0.41; P = 0.01) and age and dose (r = -0.53; P = < 0.001) and a positive correlation between liver volume and dose (r = 0.49; P = 0.002). There was no significant correlation between dosage and (R)- and (S)-warfarin concentrations, nor between dosage and INR. 3. The regression model including both age and liver volume data showed a better fit for estimation of warfarin dosage requirement than regression models based on age and liver volume data alone. Ninety-five per cent prediction intervals for warfarin dose requirements were wide, whether age alone, or age and liver volume were used in calculations. 4. Due to inter-individual variation in warfarin dosage requirements related to other influences, both explained and unexplained, routine measurement of age and liver volume would not contribute further clinically useful information to that obtained by the INR test currently used for predicting warfarin dosage requirements.
Wynne
H
H
Department of Pharmacological Sciences, University of Newcastle upon Tyne.
Cope
L
L
Kelly
P
P
Whittingham
T
T
Edwards
C
C
Kamali
F
F
D017677:Age Distribution; D000367:Age Factors; D000368:Aged; D005260:Female; D006801:Humans; D008099:Liver / Q000187:drug effects* / Q000378:metabolism*; D008297:Male; D008433:Mathematics; D008875:Middle Aged; D008954:Models, Biological; D014838:Volunteers; D014859:Warfarin / Q000493:pharmacokinetics* / Q000494:pharmacology*
D014859:Warfarin