Pharmacokinetics and safety of a new bioengineered thrombolytic agent, human tissue urokinase type plasminogen activator in Chinese healthy volunteers.
Author(s): Liang YG, Liu P, Gao HZ, Li HY, Hao GT, Wang XF, Zhang XG, Meng QY, Liu ZY
Affiliation(s): Department of Pharmacology, Affiliated Hospital of Academy of Military Medical Sciences, 8 Dongda Street, Fengtai District, Beijing, 100071, China. firstname.lastname@example.org
Publication date & source: 2011-01, Eur J Drug Metab Pharmacokinet., 35(3-4):97-102. Epub 2010 Dec 29.
Publication type: Randomized Controlled Trial
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-infinity 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.