ABSTRACT
LY01008 was a biosimilar of Avastin® developed by Shandong Boan Biotechnology. To support the clinical trial and marketing application of LY01008 as a biosimilar, a series of non-clinical pharmacodynamics (PD), pharmacokinetics (PK), and toxicological studies have been conducted. The PD study results showed that LY01008 had similar pharmacodynamic effects with Avastin in VEGF (vascular endothelial growth factor) binding activity, inhibitory effect on angiogenesis and vascular permeability, and anti-tumor activities in nude mouse models alone or combined with chemotherapeutic agents. PK study showed that LY01008 had similar PK parameters with Avastin at the same doses, and the relative bioavailability of LY01008 was 111.4%. The maximum tolerated dose of LY01008 in the single-dose toxicity study of cynomolgus monkeys was greater than 258 mg/kg. LY01008 had no effects on central nervous system, cardiovascular system and respiratory system in cynomolgus monkeys. LY01008 had no hemolytic effect in vitro and no local irritation in cynomolgus monkeys. The immunogenicity of LY01008 was no higher than that of Avastin in cynomolgus monkeys. In the one-month multiple-dose toxicity study in cynomolgus monkeys, the toxicokinetics profiles of LY01008 was similar with Avastin, the characteristics of the toxic reactions were the same and the extent was similar between LY01008 and Avastin, and no new toxic reactions were observed on LY01008. In conclusion, LY01008 had a good safety profile, and was biosimilar with Avastin in the comparative studies of pharmacodynamics, pharmacokinetics, toxicokinetics and toxicology, which supported the clinical trial and marketing application of LY01008 as a biosimilar of Avastin.
Subject(s)
Biosimilar Pharmaceuticals , Animals , Mice , Bevacizumab/toxicity , Biosimilar Pharmaceuticals/toxicity , Macaca fascicularis , Vascular Endothelial Growth Factor A , Biological Availability , Mice, NudeABSTRACT
Objective To evaluate the result of fresh autologuos pericardium for the reconstruction of new pulmonary arterial root in arterial switch operation (ASO). Methods Between January 2004 and June 2010, 63 consecutive infants with congenital heart disease were treated with ASO. A new pulmonary arterial root was reconstructed with a fresh autologuos pericardium which clipped pants-like. The followed up time was 3 months to 6 years after discharge. Patients were reexamined consecutively at 3- and 6-month; 1-, 2- and 6-year. Two-dimensional echocardiography was performed for measuring the pulmonary artery diameter. The pulmonary arterial blood speed was measured by continuous Doppler during systole. The pulmonary flow and the pulmonary artery diameter of healthy children of same age were also measure as control group. Simplified Bernoulli formula was adopted to calculate the pressure gradient through pulmonary artery anastomose for, evaluating whether it had pulmonary stenosis or not. Results Fifty seven infants were cured and discharged. Forty nine patients were finished follow up with a mean duration of( 18 ±4) months. The blood speed in the pulmonary artery anastomosis was 0.70 -2.16 m/s with a mean of (1.31 ±0.40) m/s. No pulmonary stenosis was found with the simplified Bernoulli formula. There was no significant difference regarding the pulmonary diameter and the pulmonary artery flow velocity as compared with the normal children of the same age. Conclusion The fresh autologuos pericardium is reliable for reconstruction of new pulmonary arterial root in ASO.
ABSTRACT
Objective To study the therapeutic effects of prostaglandin E1 on the neonates with transposition of the great vessels with intact ventricular septum (TGV/IVS) retrospectively. Method From January 2004 to June 2009, 34 neonates with TGV/IVS were enrolled in this study. The pulse rate and oxygen saturation (SpO2) of patients were measured percutaneouly at admission. Lipo-prostaglandin E1 (Lipo-PGE1) was administered via peripheral vein with pumping infusion continuously after diagnosis by echocardiography in order to keep the ductus arteriosus (DA) patent. The dose and the time required for the Lipo-PGEl to produce effect were recorded. The changes of SpO2 before and after administration of Lipo-PGE1 were observed. The changes of DA's diameter detected by using echocardiography before and during the operation. Results In all patients the initial dose of Lipo-PGEl was 5 ng/( kg·min) except 3 patients whom larger dosed were required to give guided by the change of SpO2 with 10 ng/(kg·min) in two patients and 15 ng/(kg·min) in one patient. The time required for Lipo-PGE to produce the effect was 5-15 minutes in most infants with mean of (12 ± 3) minutes. The mean SpO2 of the patients measured at admission was (80.05±7.64)%, and it was (86.41±4.83)% two hours before operation (P < 0.05). The average diameter of DA was (0.37±0.08) cm at the time diagnosis and it was (0.51 ±0.15) cm during the operation. The adverse effects occurred in two patients and one of them had apnea and was treated mechanical ventilation. Conclusions Lipo-PGE1 given by continuous pumping infusion via peripheral vein in dose of 5 ng per kilogram per minute can maintainthe DA patency and promote the systemic oxygenation and perfusion, improving the circulation and oxygenation and correcting the acidosis until the plastic surgery performed. Most of the adverse effects of PGE1 are dose related.
