title: Pharmacokinetics and bioavailability of tuftsin-derived T peptide, a promising antitumor agent, in beagles.
abstract: Tuftsin, a natural phagocytosis-stimulating tetrapeptide, had aroused much interest in tumor immunotherapy, but the poor pharmacokinetics hampered its clinical developments, for that it was extremely susceptible to degradation by enzymolysis in vivo. T Peptide (TP) was a newly designed tuftsin derivative aimed to enhance stability and was proved to have significant antitumor activity. In this study, the pharmacokinetics and bioavailability of TP was first clarified in beagles with subcutaneous administration, by using a simple and robust competitive ELISA method. Dose-dependency and non-linear dynamics of TP after single-dose (2, 6 and 18 mg kg(-1), respectively) were found, and the half-time of TP was proved to reach 1.3-2.8 h. Multiple dosing of 6 mg kg(-1) once a day for 7 days resulted in a slight accumulation (accumulation index was 1.92 ± 0.43), indicating that the dosing interval in the following clinical trial needs to be extended. The absolute bioavailability of TP was 31.1 ± 6.2% after subcutaneous administration. These results first demonstrated the pharmacokinetics and bioavailability data of TP in vivo, which illustrated the potential druggability of TP and provided useful information for the dosage regimen design in the following clinical trials, as well as a simple and feasible analytical method for clinical sample analysis.
authors.affiliation: State Key Laboratory of Drug Metabolism, Hematological Pharmacology, Beijing Institute of Transfusion Medicine, 27, Taiping Road, Beijing 100850, PR China.
authors.forename: Ruolan
authors.initials: R
authors.lastname: Gu
authors.affiliation: State Key Laboratory of Drug Metabolism, Hematological Pharmacology, Beijing Institute of Transfusion Medicine, 27, Taiping Road, Beijing 100850, PR China.
authors.forename: Yanlin
authors.initials: Y
authors.lastname: He
authors.affiliation: College of Pharmacy, Nankai University, 94, Weijin Road, Tianjin 300071, PR China.
authors.forename: Su
authors.initials: S
authors.lastname: Han
authors.affiliation: Department of Pharmacology and Toxicology, Beijing Institute of Radiation Medicine, 27, Taiping Road, Beijing 100850, PR China.
authors.forename: Shoujun
authors.initials: S
authors.lastname: Yuan
authors.affiliation: Department of Pharmacology and Toxicology, Beijing Institute of Radiation Medicine, 27, Taiping Road, Beijing 100850, PR China; Center for Clinical Laboratory, Airforce General Hospital of Chinese PLA, 30, Fucheng Road, Beijing 100142, PR China.
authors.forename: Yinghong
authors.initials: Y
authors.lastname: An
authors.affiliation: State Key Laboratory of Drug Metabolism, Hematological Pharmacology, Beijing Institute of Transfusion Medicine, 27, Taiping Road, Beijing 100850, PR China.
authors.forename: Zhiyun
authors.initials: Z
authors.lastname: Meng
authors.affiliation: State Key Laboratory of Drug Metabolism, Hematological Pharmacology, Beijing Institute of Transfusion Medicine, 27, Taiping Road, Beijing 100850, PR China.
authors.forename: Xiaoxia
authors.initials: X
authors.lastname: Zhu
authors.affiliation: State Key Laboratory of Drug Metabolism, Hematological Pharmacology, Beijing Institute of Transfusion Medicine, 27, Taiping Road, Beijing 100850, PR China.
authors.forename: Hui
authors.initials: H
authors.lastname: Gan
authors.affiliation: State Key Laboratory of Drug Metabolism, Hematological Pharmacology, Beijing Institute of Transfusion Medicine, 27, Taiping Road, Beijing 100850, PR China.
authors.forename: Zhuona
authors.initials: Z
authors.lastname: Wu
authors.affiliation: State Key Laboratory of Drug Metabolism, Hematological Pharmacology, Beijing Institute of Transfusion Medicine, 27, Taiping Road, Beijing 100850, PR China.
authors.forename: Jian
authors.initials: J
authors.lastname: Li
authors.affiliation: State Key Laboratory of Drug Metabolism, Hematological Pharmacology, Beijing Institute of Transfusion Medicine, 27, Taiping Road, Beijing 100850, PR China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Zheng
authors.affiliation: State Key Laboratory of Drug Metabolism, Hematological Pharmacology, Beijing Institute of Transfusion Medicine, 27, Taiping Road, Beijing 100850, PR China.
authors.forename: Ling
authors.initials: L
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Drug Metabolism, Hematological Pharmacology, Beijing Institute of Transfusion Medicine, 27, Taiping Road, Beijing 100850, PR China.
authors.forename: Lei
authors.initials: L
authors.lastname: Gao
authors.affiliation: State Key Laboratory of Drug Metabolism, Hematological Pharmacology, Beijing Institute of Transfusion Medicine, 27, Taiping Road, Beijing 100850, PR China. Electronic address: douguifang@vip.163.com.
authors.forename: Guifang
authors.initials: G
authors.lastname: Dou
mesh_terms: D000279:Administration, Cutaneous; D000818:Animals; D000970:Antineoplastic Agents / Q000493:pharmacokinetics*; D001682:Biological Availability; D004285:Dogs; D005260:Female; D008297:Male; D015717:Peptide T / Q000493:pharmacokinetics*; D011817:Rabbits; D014405:Tuftsin / Q000493:pharmacokinetics*
chemical_list: D000970:Antineoplastic Agents; D015717:Peptide T; D014405:Tuftsin
keywords: Antitumor agent; Bioavailability; Pharmacokinetics; T peptide; Tuftsin derivative; Tumor immunotherapy