Premium
Pharmacokinetics (PK) of lasofoxifene (LASO), a next generation selective estrogen receptor modulator
Author(s) -
Gardner M. J.,
Ouellet D.,
Bramson C.,
Roman D.,
Randinitis E.
Publication year - 2005
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1016/j.clpt.2004.12.219
Subject(s) - medicine , pharmacokinetics , urology
Background LASO is in late stage development for the treatment of osteoporosis. The clinical pharmacology of LASO was characterized in more than 20 Phase 1 studies. Methods The effects of LASO on the PK/PD of other drugs were evaluated. The effects of other drugs, food and hepatic impairment on LASO PK were studied in Phase I trials, whereas the effects of age, body weight, renal function and ethnicity were explored using a population PK approach. Results LASO PK appear to be linear over a broad range of doses. LASO is extensively metabolized with <2% of the dose excreted renally. The T1/2 at the 0.25 mg dose is 164 hr. Moderate hepatic impairment and inhibitors of CYP3A4 and CYP2D6, but not CYP2C9, only modestly increase exposure to LASO. Cholestyramine and food ingestion have no clinically significant effects on LASO PK. LASO did not affect the PK of CYP2E1 and CYP2D6 probe substrates or the PK of methylprednisolone, digoxin, or warfarin. The change in prothrombin time was slightly decreased when warfarin was co‐administered with LASO. Age, body weight, renal function and ethnicity were not clinically important predictors of LASO PK. Conclusions LASO is pharmacokinetically stable with little potential to interact with other concomitantly administered medications. Clinical Pharmacology & Therapeutics (2005) 77 , P85–P85; doi: 10.1016/j.clpt.2004.12.219