Tropical Journal of Pharmaceutical Research

Original Research Article | OPEN ACCESS

Plasma pharmacokinetic and heart distribution studies of Z-GP-EPI, a hypocardiotoxic prodrug of epirubicin

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