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Plasma Protein Binding of Letrozole, a New Nonsteroidal Aromatase Enzyme Inhibitor
Author(s) -
Colussi Danielle M.,
Parisot Carole Y.,
Lefèvre Gilbert Y.
Publication year - 1998
Publication title -
the journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.92
H-Index - 116
eISSN - 1552-4604
pISSN - 0091-2700
DOI - 10.1002/j.1552-4604.1998.tb04813.x
Subject(s) - letrozole , chemistry , blood proteins , aromatase inhibitor , plasma protein binding , human serum albumin , free fraction , aromatase , albumin , pharmacology , ex vivo , endocrinology , in vivo , medicine , in vitro , biochemistry , biology , microbiology and biotechnology , cancer , breast cancer
The protein binding characteristics of the nonsteroidal aromatase inhibitor letrozole were determined using 14 C‐labeled letrozole. The binding of letrozole in human serum was 60.1 ± 2.9% as a mean obtained in six individual sera and was similar in human plasma. The binding in human serum remained constant at concentrations of letrozole ranging from 10 to 500 ng/mL. A similar binding value in human serum was obtained using equilibrium dialysis and ultrafiltration technique. Albumin (binding 55.1 ± 1.4%) is the main protein involved in the drug binding to plasma proteins. Increases in letrozole concentration (10–500 ng/mL) had no effect on binding. Albumin binding appeared to be nonsaturable with a binding capacity of 2 L/mmol. Binding to α 1 ‐acid glycoprotein and to gamma globulins was lower than 10%. The fraction in erythrocytes with a hematocrit of 0.4 was found to be 35.2 ± 2.7%. Letrozole binding to serum proteins of rat, dog, mouse, and rabbit was approximately 10% lower than that in human serum and approximately 20% lower than that in baboons. Tamoxifen (100‐1,500 ng/mL) had no effect on the in vitro binding of letrozole. Ex vivo binding in plasma from patients after repeated administration of letrozole alone (61.4 ± 2.6%) was the same as after combined administration of letrozole and tamoxifen (60.0 ± 3.2%).