title: Pharmacokinetics and safety of a new bioengineered thrombolytic agent, human tissue urokinase type plasminogen activator in Chinese healthy volunteers.
abstract: The aim of our study was to investigate the pharmacokinetics and safety of human tissue urokinase type plasminogen activator (HTUPA) in healthy Chinese subjects after intravenous administration. Thirty-two subjects were given intravenous injection doses of 5-35 mg of HTUPA for safety evaluation. Twenty-four subjects were given 10, 20 or 30 mg HTUPA for pharmacokinetic assessment. Safety and tolerance were evaluated by monitoring adverse events, laboratory parameters, electrocardiography and vital signs. HTUPA concentration in human serum samples was determined by an enzyme-linked immunosorbent assay (ELISA) method. The main pharmacokinetic parameters were calculated by DAS software. HTUPA was generally well tolerated and in the whole study course no serious adverse events occurred. The main pharmacokinetic parameters were as follows: geometric mean [95% confidence interval, CI] for t1/2 were 1.5 (1.4, 1.6), 1.3 (1.2, 1.4), and 1.2 (1.2, 1.3) h, AUC0-t were 1.0 (0.7, 1.3), 2.1 (1.5, 2.7), and 5.6 (4.7, 6.6) mg h L(-1), AUC0-∞ were 1.1 (0.8, 1.3), 2.1 (1.5, 2.7), and 5.8 (4.7, 6.7) mg h L(-1) for 10, 20, and 30 mg group, respectively. The main pharmacokinetic parameters were not significantly different between males and females (P>0.05). No serious adverse events were reported by the subjects or revealed by clinical or laboratory examinations, suggesting the given doses were safe and well tolerated.
authors.affiliation: Department of Pharmacology, Affiliated Hospital of Academy of Military Medical Sciences, 8 Dongda Street, Fengtai District, Beijing, 100071, China. roc212@tom.com
authors.forename: Yu-guang
authors.initials: YG
authors.lastname: Liang
authors.forename: Peng
authors.initials: P
authors.lastname: Liu
authors.forename: Hong-zhi
authors.initials: HZ
authors.lastname: Gao
authors.forename: Hai-yan
authors.initials: HY
authors.lastname: Li
authors.forename: Guang-tao
authors.initials: GT
authors.lastname: Hao
authors.forename: Xiao-fang
authors.initials: XF
authors.lastname: Wang
authors.forename: Xi-gang
authors.initials: XG
authors.lastname: Zhang
authors.forename: Qing-yi
authors.initials: QY
authors.lastname: Meng
authors.forename: Ze-yuan
authors.initials: ZY
authors.lastname: Liu
mesh_terms: D000328:Adult; D019540:Area Under Curve; D002681:China; D004305:Dose-Response Relationship, Drug; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005343:Fibrinolytic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D006207:Half-Life; D006801:Humans; D007275:Injections, Intravenous; D008297:Male; D015202:Protein Engineering / Q000379:methods; D012737:Sex Factors; D012984:Software; D014568:Urokinase-Type Plasminogen Activator / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D055815:Young Adult
chemical_list: D005343:Fibrinolytic Agents; D014568:Urokinase-Type Plasminogen Activator