Abstract

DISPOSITION KINETICS AND DOSAGE REGIMEN OF TAMOXIFEN IN ADULT HEALTHY FEMALE VOLUNTEERS

Kiran Shahbaz*, Faqir Muhammad, Bilal Aslam, Kanwal Shahbaz, Ijaz Javed

ABSTRACT

Breast cancer is the second most pervasive cause of mortalities in the world and Tamoxifen is the hormone therapy of choice in premenopausal estrogen receptor positive breast cancer women and sometimes in post-menopausal women. The pharmgeonetics factors widely affect the pharmacokinetic parameters. Information regarding this anti breast cancer drug shows that bio disposition of Tamoxifen has not been widely studied in local healthy adult female subjects. Disposition kinectics and dosage regimen were investigated in eight healthy adult females of a specific age group 35-55 years. Blood samples were collected at various intervals after oral administration 20mg Tamoxifen tablet. Plasma concentrations were determined with HPLC. Plasma concentration versus time curve was analyzed with one compartment pharmacokinetic model to calculate the kinetic parameters such as Cmax and volume of distribution etc. The pharmacokinetic analysis revealed Cmax of 28.11 ± 2.11 ng/mL at mean Tmax of 7.7 hours.The mean ± SE volume of distribution was 306.6 ± 3.681 L/kg ,respectively while extrapolated zero time drug concentration of elimination phase 0.037 ± 0.005ng/mL. Mean ± SE rate constant for elimination phase was 0.12 ± 0.002 hr-1. Due to decrease in Cmax attained after single oral dose, it is recommended that dosing interval of Tamoxifen should be decreased as to attain steady state levels for pharmacotherapeutic results in breast cancer females. However, 5-10ng/mL change is due to the changes of environment, epigenetic and genetic variation between Pakistan and drug manufacturing foreign countries.

Keywords: Pharmacokinetics, Tamoxifen Dosage Regimen, Disposition Kinetics.