Abstract
The effects of organic acids, trypsin inhibitors and dietary protein on the oral availability of recombinant human granulocyte colony-stimulating factor (rhG-CSF) was investigated in rats by measuring the blood total leucocyte (BTL) counts. As organic acids, tartaric, succinic and citric acids were used at 2.30–7.68 mg/kg. Two trypsin inhibitors, soybean trypsin inhibitor (SBTI, 0.8–3.2 mg/kg) and chicken egg white trypsin inhibitor (CETI, 1.92 mg/kg), together with ovalbumin (0.80 mg/kg) as a representative of dietary proteins were employed with co-administration of citric acid (4.61 mg/kg). After intraduodenal administration of several kinds of test rhG-CSF solutions to rats, blood samples were collected for 48 h and the BTL counts were determined. The results are expressed as relative increase in BTL counts as compared to that before administration of the dose. The areas under the curves (AUC; % BTL increase × h) obtained for test solutions containing tartaric, succinic and citric acids were 2.1, 1.1 and 5.1 times greater than that of the control experiment, where rhG-CSF solution buffered with phosphate buffer (pH 6.1) was used. On administration of SBTI (3.20 mg/kg) and CETI (1.92 mg/kg) in combination with citric acid (4.61 mg/kg), the AUC values were determined to be 6.5 and 5.1 times greater than that of the control experiment, respectively. Co-administration of ovalbumin (0.80 mg/kg) with citric acid (4.61 mg/kg) also increased the AUC 6.3-fold as compared to the control. However, a low dose of SBTI (0.80 mg/kg) co-administered with citric acid did not exert a synergistic action.
Published Version
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call