Exemestane
Exemestane. Steroidal aromatase inhibitor — irreversible inactivation of CYP19A1 (vs the reversible non-steroidal AIs anastrozole + letrozole).… Oral half-life 24 h.
Steroidal aromatase inhibitor — irreversible inactivation of CYP19A1 (vs the reversible non-steroidal AIs anastrozole + letrozole). Adjuvant or sequential therapy in postmenopausal ER-positive breast cancer.
PK: F 0.42 IS AN ABSORBED FRACTION, AND ITS SOURCE SAYS SO. The label states "Approximately 42% of radiolabeled exemestane was ABSORBED from the gastrointestinal tract", while the European summary settles the question outright: "The absolute bioavailability in humans is unknown, although it is anticipated to be limited by an extensive first pass effect." The numeral 42 appears three times in that label, twice as an excretion fraction. The volume is explicitly apparent in the same document — "The volume of distribution of exemestane, NOT CORRECTED FOR THE ORAL BIOAVAILABILITY, is ca 20000 l" — so pairing it with an independent F divided by an availability twice, and F is pinned to 1. That alone brings implied clearance to 578 L/h against a verbatim "Oral clearance of exemestane averaged 602 L/h based on an average plasma exemestane AUC of 41.5 microg h/L", with two further sources landing at 604 and 599. The previously cited study supports none of the four values and is kept only as the fed-state bioequivalence citation. A RESIDUAL IS RECORDED SO NOBODY CHASES IT: even at F 1 the model peak is far below observation, because 20,000 L is the terminal-phase volume of a drug its own label says declines polyexponentially, and one compartment can match this drug exposure or its peak but not both. A TRAP IS ALSO RECORDED: a transdermal proliposome paper quotes "bioavailability (42%)" secondhand, laundering the label absorbed fraction.
Pharmacokinetics
- Oral — t½ 24 h · F 100% · Vd 20000 L
Sources: PMID:20329658