• Biomolecules & Therapeutics
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• v.10 no.2
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• pp.114-116
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• 2002

This study was performed to investigate the acute toxicity of PEG-hemoglobin SB1, a blood substitute, in beagle dogs. The male and female dogs were administered intravenously at the doses of 0.4375, 0.875 and 1.75 g/kg body weight, respectively. After a single intravenous administration of SB1 to dogs, we observed them daily for 2 weeks. SB1 did not induce any toxic signs in the mortalities, clinical signs, body weight changes, and gross necropsy findings of dogs. Based on these results, acute toxicity, dogs SB1 may have no side effect and its $LD_{50}$ value may be over 1.75 g/kg (25 ml/kg) of body weight in dogs.

• Biomolecules & Therapeutics
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• v.7 no.2
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• pp.170-177
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• 1999

PEG-hemoglobin SB1 (SB1), which is a hemoglobin-based oxygen carrier, is intended to use as a safe blood substitute against brain ischemia and stroke. The general pharmacological profiles of SB1 were studied. The doses given were 0, 5, 10, 20 ml/kg and drugs were administered intravenously. The animals used for this study were mouse, rat and guinea pig. SB1 showed no effects on general behavior, motor coordination, spontaneous locomotor activity, hexobarbital sleeping time, anticonvulsant activity, analgesic activity, blood pressure and heart rate, left ventricular peak systolic pressure, left ventricular end diastolic pressure, left ventricular developing pressure, double product, heart rate, coronary flow rate, smooth muscle contraction using guinea pig ileum, gastrointestinal transport, gastric secretion, urinary volume and electrolyte excretion at all doses tested except the decrease of body temperature. These findings demonstrated that SB1 possesses no general pharmacological effects at all doses tested.

• Archives of Pharmacal Research
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• v.27 no.2
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• pp.259-264
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• 2004

The purpose of the present study was to investigate the pharmacokinetics of PEG-hemoglobin SB 1, a modified bovine hemoglobin with polyethylene glycol, after its single and multiple administration in beagle dogs. For this purpose, the analytical method of free hemoglobin in the plasma was developed and validated. Excellent linearity ($r^2$=0.999) was observed in the calibration curve data, with the limit of quantification of 0.005 g/dL. The precision and the deviation of the theoretical values for accuracy were always within $\pm$15％ in both the between-and the within-day results. The method was tested by measuring the plasma concentrations following intravenous administration to beagle dogs and was shown to be suitable for pharmacokinetic studies. In a single dose study, the plasma half-life (t$_{1}$2/) increased and the total body clearance (Cl$_{t}$) decreased with the dose (i.e., 0.017 to 0.75 gHb/kg as PEG-hemoglobin SB1) in both sexes. The volume of distribution at steady-state (Vd$_{ss}$ ) showed no difference with the dose. In contrast, the values of t$_{1}$2/, CL$_{t}$ and the area under the plasma concentration-time curve (AUC) after the multiple dose were significantly different from those of the single dose administration. The values of t$_{1}$2/ in the multiple administration were about two times higher-than that of the single dose. As a result, t$_{1}$2/ of hemoglobin after the administration of PEG-hemoglobin SB1 was about 15-30 h, indicating the PEG modification of the hemoglobin lead to a prolongation of plasma concentration of the protein. Therefore, these observations suggested that the PEG modification of hemoglobin is potentially applicable in the hemoglobin-based therapeutics.tics.

• YAKHAK HOEJI
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• v.44 no.3
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• pp.232-236
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• 2000

An intravenous pharmacokinetics for a new red cell substitute, PEG-hemoglobin SB1, was studied in SD rats. Total-hemoglobin and its metabolite methemoglobin in the plasma were determined using a spectrophotometer. The limit of quantitation was 0.01g/dL and the C.V for interday assay reproducibility was less than 6%. Upon intravenous administration of anticipated clinical dose, 10 ml(0.7 gHb)/kg, plasma concentration curve of total-hemoglobin was well described by one-compartment model. The $t_{\frac{1}{2}},{\;}CL_{t}$, Vd and $AUC^{0-48hr}$ were $8.23{\pm}0.96{\;}hr,{\;}0.06{\;}{\pm}{\;}0.01 {\;}dL/hr/kg,{\;}0.66{\pm}0.05{\;}dL/lg{\;}and{\;}13.6{\;}{\pm}{\;}1.01g{\cdot}hr/dL$, respectively, in male rats(n=5, $mean{\;}{\pm}{\;}SD$). Those parameters in female rats were $9.21{\;}\pm{\;}2.31{\;}hr,{\;}0.06{\;}{\pm}{\;}0.01{\;}dL/hr/kg,{\;}0.79{\pm}{\;}0.08{\;}dL/kg{\;}and{\;}13.0{\;}{\pm}{\;}2.36{\;}g{\cdot}hr/dL$, respectively. Similar kinetic profiles between males and females were also obtained from other parameters. Small amount of methemoglobin, an oxidative metabolite of SB1, was detected in the plasma of both sexes, where the $AUC^{0-48{\;}hr,m}$ and $t_{{\frac{1}{2}},m}$ were approximately $1.5{\;}g{\cdot}hr/dL$ and 20 hr, respectively. The present work provides a critical kinetic data for the effective clinical applications of PEG-hemoglobin SB1.