CONTEXT: As a class of angiogenesis inhibitors, @entity6950 conjugates have shown significant effectiveness in several studies. OBJECTIVES: The purpose of our current study is to evaluate the effectiveness and safety of infusing the low molecular weight heparin and @entity7362 (LHT7) conjugate, which have been developed as a potent angiogenesis inhibitor. METHODS: To evaluate its safety, the method of intravenous infusion was compared with its i.v bolus administration. Intravenous infusion was administered at a rate of 400  l/min/kg of body weight for 30 min. Pharmacokinetic analysis, organ accumulation, and plasma concentration profiles of LHT7 were measured. The anticancer effect of LHT7 was evaluated in @entity19 and @entity1 xenograft models, and preclinical studies were performed in SD @entity35 and @entity235 . RESULTS: The result of the pharmacokinetic studies showed reduced organ accumulation in @entity19 and the AUC(0-96h) (Area under the curve) was increased up to 1485    125 h* g/ml. The efficacy, at dose 1 mg/kg/2 days was higher for i.v infusion than for i.v bolus administration in both @entity19 and @entity1 @entity5 models. The preclinical studies showed the safety dose of LHT7 is less than 20 mg/kg in SD @entity35 and in the next safety analysis in @entity235 showed that there were no organ-specific adverse effects in higher doses, such as, 12 mg/kg. LHT7 showed sustained effects with minimized adverse events when administered through i.v infusion. CONCLUSIONS: LHT7 (i.v infusion) could be safely used for further clinical development as a multi-targeting anti-angiogenic agent.

Safety Studies on Intravenous Infusion of a Potent Angiogenesis Inhibitor: XXXX Conjugated Low Molecular Weight Heparin Derivative LHT7 in Preclinical Models.

@entity1 :: ('9606', 'Species') :: ['human'] @entity7362 :: ('MESH:D013656', 'Chemical') :: ['taurocholate'] @entity19 :: ('10090', 'Species') :: ['mice', 'murine'] @entity235 :: ('9615', 'Species') :: ['beagle dogs'] @entity5 :: ('MESH:D009369', 'Disease') :: ['cancer'] @entity6950 :: ('MESH:D006493', 'Chemical') :: ['heparin'] @entity35 :: ('10116', 'Species') :: ['rats']
@entity7362 :: (MESH:D013656,Chemical) :: ['Taurocholate']
