Pharmacokinetic Study of ZS-1, a Targeted Peptide to NCI-H1299, in Rats Following Intravenous Administration |
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Authors: | Junqiang Luo Xun Li Xuediao Pan Jie Zhou Wenbin Feng Dalu Liu Linquan Zang |
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Institution: | 1. Department of Pharmacology, Novel Drug Screening Center, Guangdong Pharmaceutical University, Guangzhou, 510006, People’s Republic of China
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Abstract: | To investigate the pharmacokinetics of ZS-1 following intravenous injection in rats, ZS-1 was administered at doses of 20, 30 and 45 mg kg?1, respectively. Blood samples were collected at 0.5, 3, 8, 12, 15, 20, 30, 40 and 45 min. ZS-1 in rat plasma was measured by LC. The limit of detection (LOD) was 0.02 μg mL?1. The relative standard deviation (RSD) of intra- and inter-day precisions were <10%, and the accuracy of intra- and inter-day were >94%. The mean extraction recovery of ZS-1 was 86.1%. After intravenous injection at doses of 20, 30 and 45 mg kg?1, the concentration–time curves of ZS-1 fitted well to one compartment model. Area under the concentration–time curves (AUC) increased with dose. Clearance rates (CL) and elimination half-lives (T 1/2) had no significant difference between different dose groups (P > 0.05). ZS-1 was stable in plasma after at 25 °C for 2, 4, 6 h, after three freeze–thaw cycles, after ?20 °C for a month, and after ?80 °C for 3 months. The accuracy of ZS-1 was between 96.8 and 106.9%. The results indicated there was no significant degradation. These data indicated that the method for analysis of ZS-1 was reliable and the pharmacokinetic data could guide dosing regimens to be tested in future clinical pharmacokinetic study. |
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