INFLUENCE OF AGE ON TOREMIFENE PHARMACOKINETICS

Toremifene pharmacokinetics were compared in ten healthy young men (< 33 years) and elderly women (< 65 years). A single oral 120-mg dose of toremifene was given after an overnight fast and blood samples were c ollected over 28 days. Serum levels of the parent drug and the metabol ites were determined; appropriate pharmacokinetic parameters were calc ulated and statistically evaluated. Toremifene peak concentrations (av erage 640 ng/ml) were achieved at 3.5 h. The area under the curve (AUC ) and the apparent oral clearance were comparable in the young and eld erly subjects. The half-life was prolonged (4.2 versus 7.2 days) and t he apparent volume of distribution was increased (457 versus 627 1) in the elderly. The peak concentration of the main metabolite N-demethyl toremifene was lower (159 versus 233 ng/ml) and the half-life was prol onged (8.3 versus 19.1 days) in the elderly subjects, but the AUC valu es were comparable. The results suggest that toremifene is distributed more widely in the elderly but that its clearance is unaffected by ag e. It is concluded that the dosage requirement of the drug is unlikely to differ between young and elderly subjects.