Age-related difference in tamoxifen disposition

Clinical Pharmacology and Therapeutics
F PeyradeG Milano

Abstract

To investigate the pharmacokinetic aspects of tamoxifen, such as the pharmacokinetic-pharmacodynamic (toxicity and clinical response) relationship and the influence of hepatic dysfunction, age, treatment duration, and associated chemotherapy on tamoxifen pharmacokinetics. Three hundred sixteen patients with breast cancer (247 postmenopausal women) were investigated. Mean age was 58 years (age range, 29 to 85 years). One hundred seventeen patients received tamoxifen as single therapy (adjuvant, 60; neoadjuvant, 17; metastatic, 40); 292 of 316 received 30 mg daily. We obtained 794 blood samples at steady state. Tamoxifen and metabolites, N-desmethyltamoxifen, N-desdimethyltamoxifen, primary alcohol, and 4-hydroxytamoxifen were measured by HPLC. Serum concentrations of tamoxifen and metabolites showed a wide asymmetrical distribution. Median and extremes were 347 nmol/L (not detectable [ND] to 1677) for tamoxifen, 572 nmol/L (ND to 3132) for N-desmethyltamoxifen, 109 nmol/L (ND to 795) for N-desdimethyltamoxifen, and 59 nmol/L (ND to 390) for primary alcohol. 4-Hydroxytamoxifen was detectable in 9.5% of the samples (ND to 162 nmol/L). Neither the absolute nor the relative concentrations of each compound showed significant variatio...Continue Reading

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