ABSOLUTE BIOAVAILABILITY OF LETROZOLE IN HEALTHY POSTMENOPAUSAL WOMEN

Letrozole is a new non-steroidal inhibitor of the aromatase enzyme sys tem. It is currently under development for the treatment of postmenopa usal women with advanced breast cancer. Absolute bioavailability of le trozole when given orally as one 2.5 mg film-coated tablet in comparis on to the same dose given intravenously as a bolus injection was studi ed in 12 healthy postmenopausal women. Letrozole absolute systemic bio availability after p.o. administration was 99.9+/-16.3%. Elimination o f letrozole was slow. Total-body clearance of letrozole from plasma af ter i.v. administration was low (2.21 L h(-1)). The calculated distrib ution volume at steady state (1.87 L kg(-1)) suggests a rather high ti ssue distribution. Biotransformation of letrozole is the main eliminat ion mechanism with the glucuronide conjugate of the secondary alcohol metabolite being the predominant species found in urine. The two study treatments were tolerated equally well. (C) 1997 John Wiley & Sons, L td.