Pharmacokinetics of oxycodone hydrochloride and three of its metabolites after intravenous administration in Chinese patients with pain.

OBJECTIVES: The aim of this study is to evaluate the pharmacokinetic profile of oxycodone and three of its metabolites, noroxycodone, oxymorphone and noroxymorphone after intravenous administration in Chinese patients with pain. METHODS: Forty-two subjects were assigned to receive intravenous administration of oxycodone hydrochloride of 2.5, 5 or 10 mg. Plasma and urine samples were collected for up to 24 h after intravenous administration of oxycodone hydrochloride. RESULTS: Pharmacokinetic parameters showed that mean values of C(max), AUC(0-t) and AUC(0-∞) of oxycodone were dose dependent, whereas Tmax and t(1/2) were not. The mean AUC(0-t) ratio of noroxycodone to oxycodone ranged from 0.35 to 0.42 over three doses, and those of noroxymorphone, or oxymorphone, to oxycodone were ranging of 0.06-0.08 and 0.007-0.008, respectively. Oxycodone and its three metabolites were excreted from urine. Approximately 10% of unchanged oxycodone was recovered in 24 h. Most adverse events (AEs) reported were mild to moderate. The frequently occurred AEs were dizziness, nausea, vomiting, drowsiness and fatigue. No dose-related AEs were found. CONCLUSION: Our pharmacokinetics of oxycodone injection in Chinese patients with pain strongly support continued development of oxycodone as an effective analgesic drug in China.

Pharmacokinetics and safety of a new bioengineered thrombolytic agent, human tissue urokinase type plasminogen activator in Chinese healthy volunteers.

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.

Single-dose safety, pharmacokinetics, and food effects studies of compound naphthoquine phosphate tablets in healthy volunteers.

The compound naphthoquine phosphate is a novel antimalaria drug tablet containing a fixed-dose combination of naphthoquine phosphate and artemisinin in a 1:2.5 ratio. A randomized, open study on the safety and tolerability was conducted in 28 healthy male volunteers using a single oral dose of 350 mg, 700 mg, 1400 mg, or 2100 mg of artemisinin-naphthoquine phosphate. Pharmacokinetics at the last 3 doses were examined in 30 volunteers. Food effects were also determined. Serial blood samples up to 216 hours after single oral dose administration were analyzed for plasma concentrations using a validated high-performance liquid chromatography-tandem mass spectrometry assay. The compound was well tolerated at single doses up to 2100 mg. Increased exposure to naphthoquine phosphate and artemisinin was less than dose proportional and linear. The half-life of naphthoquine phosphate was approximately 255 hours. The combination increased the AUC(0-t) and C(max) of both artemisinin (by 71% and 49%) and naphthoquine phosphate (by 135% and 104%) compared with monotherapy. Food intake greatly increased the AUC(0-t) of artemisinin with a ratio of 77% and reduced that of naphthoquine phosphate from 955 ± 352 µg·h/L under the fasted state to 446 ± 231 µg·h/L in the fed condition. The pharmacokinetics and safety profile of the drug support its continued investigation in future clinical studies.