TOTAL BODY CLEARANCE AND MEAN RESIDENCE TIME OF TAMOXIFEN IN FEMALE HEALTHY SUBJECTS
Keywords:Total body clearance, mean residence time, tamoxifen body clearance, total body clearance breast cancer medicine.
Objective: To investigate total body clearance and mean residence time after single oral dose of tamoxifen in female healthy subjects focusing on two concepts pharmenzymonetics and pharmgeonetics for the first time in Pakistan.
Methodology: Two parameters were investigated in eight healthy female subjects after single oral dose of 20mg tablet Nolvadex brand. Blood samples were collected and plasma concentration was determined by Gradient HPLC method to evaluate the total body clearance and mean resident time. Subjects were kept under observation for 4 weeks detecting any adverse signs or symptoms.
Results: Value of total body clearance mean ±SE was 39.7 ± 0.55 L/Hr/Kg and that of mean residence time MRT is 15.18 ± 0.19 Hours. There were no adverse signs reported during 4 weeks of direct observation of subjects after oral single dose. Blood pressure, temperature, pulse rate and appearant activity of subjects remained normal.
Conclusion: The total body clearance and MRT of tamoxifen is greater as compared to literature value in the healthy females of Pakistan due to pharmgeonetics.
Abraham J, M Maranian1, K E Driver1, R Platte, B Kalmyrzaev1, C Baynes, C Luccarini, M Shah1, S Ingle, D Greenberg, HM Earl, AM Dunning1, P Pharoah, C Caldas, (2010). CYP2D6 gene variants: association with breast cancer specific survival in a cohort of breast cancer patients from the United Kingdom treated with adjuvant Tamoxifen. Breast Cancer Research, 12:R64.
Adam HK, JS Patterson, JV Kemp (1980). Studies in the metabolism and pharmacokinetics of Tamoxifen in normal volunteers. Cancer Treat Rep 64: 761
Baggot JD, (1977). Principles of drug disposition in domestic animals: The basis of veterinary Clinical Pharmacokinetics. W.B. Saunders Co., 199 Ed, Philadelphia,: 72-74.
Berliere, M., Duhoux, F. P., Dalenc, F., Baurain, J. F., Dellevigne, L., Galant, C., ... & Machiels, J. P. (2013). Tamoxifen and ovarian function.
Dickschen K, Stefan W, Kirstin T, Jörg Lippert, Georg Hempel,and Thomas Eissing. (2012). Physiologically Based Pharmacokinetic Modeling of Tamoxifen and its Metabolites in Women of Different CYP2D6 Phenotypes Provides New Insight into the Tamoxifen Mass Balance. Pharmacol, 3: 92
Golander Y, LA Sternson (1980). Paired-ion chromatographic analysis of Tamoxifen and two major metabolites in plasma. J Chromatogr 181: 41.
Javed I, Z Iqbal, ZRahman, MZ Khan, MFaqir, BAslam, M A Sandhu and JI Sultan. (2009). Disposition kinetics and optimal dosage of ciprofloxacin healthy domestic ruminant species. Actavet Benro 78: 155-162.
Kashtiaray K, H Farahani, Farhadi1, B Rochatand HR Sobhi. (2011). Trace Determination of Tamoxifen in Biological Fluids Using Hollow Fiber Liquid-Phase Microextraction Followed by High-Performance Liquid Chromatography-Ultraviolet Detection. Am J of Anal Chem, 2: 429-436.
Li XF, S Carter, NJ Dovichi, JY Zhao, P Kovarik and T Sakuma, (2001). Analysis of Tamoxifen and its metabolites in synthetic gastric fluid digests and urine samples using high-performance liquid chromatography with electrospray mass spectrometry. J Chromatogr A, 914: 5-12.
Lien EA, Anker G, Lønning PE, Solheim E, Ueland PM (1990) Decreased serum concentrations of Tamoxifen and its metabolites induced by aminoglutethimide. Cancer Res 50: 5851.
Shahbaz, K., Mehfooz, A., & Khadam, W. (2014). Breast Cancer Vaccination-An Envisioned Future. Indo American Journal of Pharmaceutical Research, 4(3), 1580-1585.
Shahbaz, K. (2015). Comparison Between Standard Treatment Guidelines Of Preeclampsia Proposed By Who And Current Practice In Tertiary Care Centers. J. PP. Sci, 4(8), 1566-1593.
Zhu YB, Q Zhang, JJ Zou, CX Yu,DW Xiao, (2008), Optimizing high-performance liquid chromatography method with fluorescence detection for quantification of tamoxifen and two metabolites in human plasma: application to a clinical study. J Pharm Biomed Anal.46:349-55.
How to Cite
This work is licensed under a Creative Commons Attribution-NoDerivatives 4.0 International License.