ABSORPTION OF RECOMBINANT HUMAN GRANULOCYTE-COLONY-STIMULATING FACTOR (RHG-CSF) FROM RAT NASAL-MUCOSA

被引:28
作者
MACHIDA, M
SANO, K
ARAKAWA, M
HAYASHI, M
AWAZU, S
机构
[1] TOKYO COLL PHARM, DEPT BIOPHARMACEUT, 1432-1 HORINOUCHI, HACHIOJI, TOKYO 19203, JAPAN
[2] CHUGAI PHARMACEUT CO LTD, DIV DEV & TECHNOL, FORMULAT TECHNOL LAB, TOSHIMA KU, TOKYO 171, JAPAN
关键词
GRANULOCYTE COLONY-STIMULATING FACTOR (RHG-CSF); RECOMBINANT HUMAN GRANULOCYTE-CSF; NASAL ABSORPTION IN RATS; BIOAVAILABILITY; LEUKOCYTE NUMBER;
D O I
10.1023/A:1018990318090
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
Nasal absorption of recombinant human granulocyte colony-stimulating factor (rhG-CSF) was examined in the rat. The relative bioavailability of rhG-CSF for subcutaneous administration was approximately 2%, as evaluated from the immunologically active rhG-CSF concentration in rat plasma and the area under the curve (AUC) of the plasma rhG-CSF concentration versus time for 8 hr. Pharmacological availability relative to subcutaneous administration was determined from the increase in total blood leukocyte numbers. The pharmacological availability was 5-10%, determined from the AUC for the increased ratio of total leukocyte numbers versus time for 48 hr; it was slightly dependent on the pH and the osmotic pressure of the dosing solution. Accordingly, the plasma concentration of rhG-CSF did not always reflect its pharmacological effects. Relative bioavailability and pharmacological availability were increased about 23 times and 3 times, respectively, by polyoxyethylene 9-lauryl ether (Laureth-9), but no increase in availability occurred with sodium glycocholate. The increase in total leukocyte numbers was maintained during multiple rhG-CSF dosing, and the addition of Laureth-9 further increased the pharmacological effects of this agent. This study indicates that nasal administration of rhG-CSF is an effective parenteral administration route.
引用
收藏
页码:1372 / 1377
页数:6
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