ABSTRACT
AIM: To established an HPLC/MS/MS method for the study of pharmcokinetics of PMEA-Na (the mono-sodium salts of 9-[2-(phosphonomethoxy) ethyl] adenine) in beagle dogs. METHODS: PMEA-Na and internal standard 9-(3-phosphony-methoxypropyl) adenine were isolated from plasma by protein precipitation with methanol, and then analyzed adopting multiple reaction monitoring (MRM) mode. Using Xterra MS column, the mobile phases consisted of methanol:water:formic acid (25:75:0.5) at a flow rate of 0.25 ml·min-1. Beagle dogs received the intravenous dosage of PMEA-Na at 1.0, 3.0 and 6.0 mg·kg-1. Pharmacokinetic parameters were obtained from concentration-time curves by non-linear least-squares regression using the program DAS. RESULTS: The linear calibration curve was obtained in the concentration range of 0.02 to 20 mg·L-1 (r=0.999), and the limit of quantitition was 20 μg·L-1. The within-day and internal-day precisions (RSD) were less than 6.5% and 10.8%, respectively. The accuracy was 97.1%～107.3%. After a single dose studies in dogs the AUC were 2.3±0.5, 8.2±1.3 and 18.5±1.3 mg·L-1·h; the t1/2 were 3.9±1.8, 8.4±1.5 and 8.9±0.6 h; the CL were 0.44±0.09, 0.35±0.05 and 0.31±0.03 ml·h-1·kg-1 at the dose level of 1.0, 3.0 and 6.0 mg·kg-1 respectively. CONCLUSION: The analytical method is sensitive and specific for investigation the pharmacokintics of PMEA-Na in beagle dogs.
ABSTRACT
AIM To provide toxicokinetics data for toxicity studies of repeated doses of sodium 9-[2-(phosphonomethoxy) ethyl] adenine (PMEA-Na). METHODS The concentrations of PMEA-Na in plasma and urine were determined by HPLC/MS/MS method after single and multiple iv administrations in dogs. Data were executed by the statistical moment method to acquire the toxicokinetics parameters. Serum biochemical tests and histopathological examination were performed. RESULTS The system exposure of PMEA-Na in dogs was dose-dependent over the dose range of 1.0-6.0 mg·kg-1. The areas under the plasma concentration-time curve of PMEA-Na after single and multiple iv administrations at 1.0, 3.0 and 6.0 mg·kg-1 dosage were (2.3±0.5), (8.4±1.6), (17.5±3.7) and (5.0±0.4), (15.9±3.2), (30.3±4.7)mg·L-1·h, respectively. The urinary excretion of PMEA-Na in 72 h after iv administration was (87.0±4.8)% at the dose of 3.0 mg·kg-1. In 6.0 mg·kg-1 dose group, liver enzyme activity of glutamic-pyruvic transaminase and serum levels of total bilirubin, blood urea nitrogen, creatinine and triglycerides were all significantly elevated; glucose level significantly decreased comparing with the control group. Histopathological observation showed distinct pathological changes in liver and kidney tissues of 6.0 mg·kg-1 dose group. CONCLUSION There was evidence of toxicity after repeated-dose (14 d) of PMEA-Na in dogs and the major toxicity target organs were the kidney and liver.
ABSTRACT
ETAN is a marine biomaterial which is made of chitosan,a partially deacetylated derivative of chitin ,and prepared by a foaming technique. The effects of absorbing exudate, stopbleeding,promoting wound healing and biological compatibility were observed in this experiment. The results showed ETAN could promote skin wound healing reduce the scab time of the wound surfaces. Skin tissue was healed quickly after ETAN was coated on wound skin surfaces,and it had marked effects of absorbing exudate,and haemostasis. Its effects were superior to that of gelatin sponge. ETAN could be fused with subcutaneous tisssue embeded subcutaneously two weeks later. The fused skin tissue was returned to normal skin tissue nearly after it was embeded four weeks . These experimental results showed ETAN had a better biological compatibility.
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This article reports preliminarily the effects on the antibacterial activity & cytotoxicity of the derivatives of two diterpenoid components, Amethystoidin A & Rabdosia macrophylla C(i.e.Orido-nin ) which were isolated from the medicinal plants of Rabdosia ( Bl. ) Hassk. The experiment demonstrated that diacetate derivative of Amethystoidin A ( n ) could significantly enhance the antibacterial effect being 2 - 3 times more potent than that of Amethystoidin A. Hydrolytic derivative of Rabdosia macrophylla C (V) had a significant increase in the cytotoxicity on heptoma cell (QGY-7703 ) in vitro.