The effects of testosterone undecanoate on the functional activity of P-glycoprotein (ABCB1 protein) were studied in male Chinchilla rabbits. Testosterone was given as single intramuscular doses of 12 or 24 mg/kg. The functional activity of P-glycoprotein was determined in terms of the pharmacokinetics of its marker substrate - fexofenadine - on days 7, 14, and 21 after hormone administration. Administration of testosterone at a dose of 12 mg/kg (n = 7) increased the C max of fexofenadine on days 7 and 14 and AUC 0-t on day 14 and decreased total clearance on day 14. Use of testosterone at a dose of 24 mg/kg (n = 7) led to increases in the C max of fexofenadine on day 7 and AUC 0-t on days 7, 14, and 21 and decreased total clearance on days 7 and 14. These changes in the pharmacokinetics of fexofenadine provide evidence of decreases in the functional activity of Pgp on the background of testosterone administration. Correlational relationships were found between measures of the pharmacokinetics of fexofenadine and serum testosterone levels.
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References
V. G. Kukes, S. V. Grachev, D. A. Sychev, and G. V. Ramenskaya, Drug Metabolism. Scientific Basis of Personalized Medicine: Guidelines for Doctors [in Russian], GEOTAR- MEDia, Moscow (2008).
E. N. Yakusheva, I. V. Chernykh, A. V. Shchul’kin, and N. M. Popova, Usp. Fiziol. Nauk, 45(4), 90 – 99 (2014).
V. Poongavanam, N. Haider, and G. F. Ecker, Bioog. Med. Chem., 20(18), 5388 – 5395 (2012).
D. Surajit, G. Sriram, and A. K. Mitra, JPET, 311(1), 246 – 255 (2004).
C. K. van Kalken, H. J. Broxterman, H. M. Pinedo, et al., Br. J. Cancer, 67(2), 284 – 289 (1993).
C. Zhao, D. G. Moon, and J. K. Park, Can. Urol. Assoc. J., 7(3 – 4), 221 – 225 (2013).
E. N. Yakusheva, A. V. Shchul’kin, I. V. Chernykh, and D. S. Titov, Ros. Med.-Biol. Vestn. im. Akad. I. P. Pavlova. No. 2, 74 – 77 (2014).
U. S. Food and Drug Administration, Center for Drug Evaluation and Research, Guidance for Industry: Drug Interaction Studies. Study Design, Data Analysis, Implications for Dosing and Labeling Recommendations; Available at: http: //www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/ucm292362.pdf.
M. Molimard, B. Diquet, and M. S. Benedetti, Fund. Clin. Pharmacol., 18(4), 399 – 411 (2004).
E. G. Schuetz, K. N. Furuya, and J. D. Schuetz, J. Pharmacol. Exp. Ther., 275, 1011 – 1018 (1995).
S. Drescher, E. Schaeffeler, M. Hitzl, et al., Br. J. Clin. Pharmacol., 53(5), 526 – 534 (2002).
T. Suzuki, Y. L. Zhao, M. Nadai, et al., Life Sci., 79(5), 455 – 461 (2006).
L. Salphati and L. Z. Benet, Biochem. Pharmacol., 55(4), 387 – 395 (1998).
C. MacLean, U. Moenning, A. Reichel, and G. Fricker, Drug Metab. Dispos., 36(7), 1249 – 1254 (2008).
E. N. Yakusheva, I. V. Chernykh, A. V. Shchul’kin, et al., Ros. Fiziol. Zh. im. I. M. Sechenova, 100(8), 944 – 952 (2014).
K. S. Fenner, M. D. Troutman, S. Kempshall, et al., Clin. Pharmacol. Therap., 85(2), 173 – 181 (2009).
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Translated from Khimiko-Farmatsevticheskii Zhurnal, Vol. 51, No. 9, pp. 3 – 7, September, 2017.
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Shchul’kin, A.V., Yakusheva, E.N., Chernykh, I.V. et al. Effects of Testosterone on the Functional Activity of P-Glycoprotein. Pharm Chem J 51, 743–747 (2017). https://doi.org/10.1007/s11094-017-1685-1
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DOI: https://doi.org/10.1007/s11094-017-1685-1