| Autor: |
Sandberg JA; Ribozyme Pharmaceuticals, Inc., Boulder, CO 80301, USA., Sproul CD, Blanchard KS, Bellon L, Sweedler D, Powell JA, Caputo FA, Kornbrust DJ, Parker VP, Parry TJ, Blatt LM |
| Jazyk: |
angličtina |
| Zdroj: |
Antisense & nucleic acid drug development [Antisense Nucleic Acid Drug Dev] 2000 Jun; Vol. 10 (3), pp. 153-62. |
| DOI: |
10.1089/oli.1.2000.10.153 |
| Abstrakt: |
The potential acute toxicity of a ribozyme (ANGIOZYME) targeting the flt-1 vascular endothelial growth factor (VEGF) receptor mRNA was evaluated in cynomolgus monkeys following i.v. infusion or s.c. injection. ANGIOZYME was administered as a 4-hour i.v. infusion at doses of 10, 30, or 100 mg/kg or a s.c. bolus at 100 mg/kg. End points included blood pressure, electrocardiogram (ECG), clinical chemistry, hematology, complement factors, coagulation parameters, and ribozyme plasma concentrations. ANGIOZYME was well tolerated, with no drug-associated morbidity or mortality. There was no clear evidence of ANGIOZYME-related adverse effects in this study. Slight increases in spleen weight and lymphoid hyperplasia were observed in several animals. However, these changes were not dose dependent. Steady-state concentrations of ANGIOZYME were achieved during the 4-hour infusion of 10, 30, or 100 mg/kg. Dose-dependent elimination of ANGIOZYME was observed, with faster clearance at the two highest doses. ANGIOZYME was slowly absorbed after s.c. administration, resulting in steady-state concentrations for the 9-hour sampling period. Monkeys in this toxicology study received significant plasma ANGIOZYME exposure by both the s.c. and i.v. routes. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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