Tamoxifen and its main metabolites serum and tissue concentrations in breast cancer women.
Because of a possible relationship between tamoxifen (T) concentrations and clinical effects, we initiated a preliminary investigation on serum and tissue concentrations of T and its main active metabolites, and 4-hydroxytamoxifen, in women with positive breast cancer estrogen receptor. One hundred forty-eight patients were studied: 80 were admitted for monitoring of therapeutic serum drug concentrations, 22 had tissue concentrations taken at surgery, and 46 patients had uterine mucosa levels measured at diagnostic hysteroscopy. Steady-state serum concentrations were reached after 1 month of continuous treatment, with desmethyltamoxifen being the highest represented derivative from the third week onward. There was no relationship between dose (in mg/kg body weight) and steady-state serum concentrations during therapeutic drug monitoring of patients. The highest tissue concentrations were observed in breast lymph-nodes, cancer tissue, and uterine mucosa. On the basis of these data, we speculate that T and its active metabolites may exert both a defensive role (ie, an obstacle to the diffusion of malignant cells through the local lymphatic system) and a harmful one (induction of uterine malignancies).
Furlanut
Mario
M
Institute of Clinical Pharmacology and Toxicology, DPMSC, University of Udine, Udine, Italy. mario.furlanut@med.uniud.it
Franceschi
Loretta
L
Pasqual
Enrico
E
Bacchetti
Stefano
S
Poz
Donatella
D
Giorda
Giorgio
G
Cagol
Pierpaolo
P
D000368:Aged; D001943:Breast Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D016903:Drug Monitoring / Q000379:methods; D005260:Female; D006801:Humans; D008198:Lymph Nodes / Q000378:metabolism*; D008875:Middle Aged; D020845:Selective Estrogen Receptor Modulators / Q000097:blood / Q000378:metabolism* / Q000627:therapeutic use; D013629:Tamoxifen / Q000097:blood / Q000378:metabolism* / Q000627:therapeutic use; D014018:Tissue Distribution
D020845:Selective Estrogen Receptor Modulators; D013629:Tamoxifen