Guangquan Liu,
Enpan Mo,
Xiaoxiong Wang,
Nong Wu,
Fanglan Liu,
Weiqi Yuan,
Huaqing Chen,
Jingjing Wang,
Jun Xu,
Shaohui Cai
College of Pharmacy, Jinan University, Guangzhou 510632, China;
For correspondence:- Shaohui Cai
Email: csh5689@sina.com Tel:+8602085228025
Received: 12 February 2015
Accepted: 26 April 2015
Published: 26 May 2015
Citation:
Liu G, Mo E, Wang X, Wu N, Liu F, Yuan W, et al.
Plasma pharmacokinetic and heart distribution studies of Z-GP-EPI, a hypocardiotoxic prodrug of epirubicin. Trop J Pharm Res 2015; 14(5):899-905
doi:
10.4314/tjpr.v14i5.21
© 2015 The authors.
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Abstract
Purpose: To explore the plasma pharmacokinetics and heart distribution of Z-GP-EPI, a low cardiotoxic prodrug of epirubicin (EPI).
Methods: The drugs were administered to 20 rats (11. 22, 44 µmol/kg) by intravenous injection and 70 mice (30 µmol/kg) by tail intravenous injection. The profiles of Z-GP-EPI and EPI in rat plasma or mice heart were determined by high performance liquid chromatography (HPLC) method, which employed the Octadecylsilyl (ODS) column with a mobile phase of acetonitrile : 0.1 % trifluoroacetic-water (42:58, v/v) at a flow rate of 1.0 mL/min and an ultraviolet (UV) detector at a wavelength of 495 nm. Pharmacokinetics parameters were calculated using a pharmacokinetic software.
Results: Relative standard deviation (RSD) of intra- and inter-day precision values was < 15 % in each case while method accuracy with recovery was between 85 and 110 % for plasma and heart samples. After administration of 22 umol/kg Z-GP-EPI or EPI, terminal elimination half-life (t1/2) of Z-GP-EPI (1.41 h) was smaller than that of EPI (12.24 h). Furthermore, the concentration of Z-GP-EPI in heart rapidly decreased from 17.3 µg/g (0.05 h) to undetectable levels (2 h) while EPI changed from 14.3 µg/g (0.05 h) to 9.5 µg/g (2 h).
Conclusion: The HPLC method established in this study is a feasible approach to detecting Z-GP-EPI and EPI in plasma and heart tissue. In addition, Z-GP-EPI is eliminated more rapidly from plasma and heart tissue than EPI, which probably contributes to the low cardiotoxicity of Z-GP-EPI.
Keywords: N-Benzyloxycarbony-prolinyl-glycinyl epirubicin (Z-GP-EPI), Epirubicin, Prodrug, Hypocardiotoxic, Pharmacokinetics, Heart distribution